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1.
Article in Chinese | WPRIM | ID: wpr-1013441

ABSTRACT

Background The active metabolite of benzo[a]pyrene (BaP), 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), can form adducts with DNA, but the spectrum of BPDE-DNA adducts is unclear. Objective To identify the distribution of BPDE adduct sites and associated genes at the whole-genome level by chromatin immunoprecipitation followed by sequencing (ChIP-Seq), and serve as a basis for further exploring the toxicological mechanisms of BaP. Methods Human bronchial epithelial-like cells (16HBE) were cultured to the fourth generation inthe logarithmic growth phase. Cells were harvested and added to chromatin immunoprecipitation lysis buffer. The lysate was divided into experimental and control groups. The experimental group received a final concentration of 20 μmol·L−1 BPDE solution, while the control group received an equivalent volume of dimethyl sulfoxide solution. The cells were then incubated at 37 °C for 24 h. Chromatin fragments of 100-500 bp were obtained through sonication. BPDE-specific antibody (anti-BPDE 8E11) was used to enrich DNA fragments with BPDE adducts. High-throughput sequencing was conducted to detect BPDE adduct sites. The top 1000 peak sequences were subjected to motif analysis using MEME and DREME software. BPDE adduct target genes at the whole-genome level were annotated, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of BPDE adduct target genes were conducted using bioinformatics techniques. Results The high-throughput sequencing detected a total of 842 BPDE binding sites, distributed across various chromosomes. BPDE covalently bound to both coding and non-coding regions of genes, with 73.9% binding sites located in intergenic regions, 19.6% in intronic regions, and smaller proportions in upstream 2 kilobase, exonic, downstream 2 kilobase, and 5' untranslated regions. Regarding the top 1000 peak sequences, four reliable motifs were identified, revealing that sites rich in adenine (A) and guanine (G) were prone to binding. Through the enrichment analysis of binding sites, a total of 199 BPDE-adduct target genes were identified, with the majority located on chromosomes 1, 5, 7, 12, 17, and X. The GO analysis indicated that these target genes were mainly enriched in nucleic acid and protein binding, participating in the regulation of catalytic activity, transport activity, translation elongation factor activity, and playing important roles in cell division, differentiation, motility, substance transport, and information transfer. The KEGG analysis revealed that these target genes were primarily enriched in pathways related to cardiovascular diseases, cancer, and immune-inflammatory responses. Conclusion Using ChIP-Seq, 199 BPDE adduct target genes at genome-wide level are identified, impacting biological functions such as cell division, differentiation, motility, substance transport, and information transfer. These genes are closely associated with cardiovascular diseases, tumors, and immune-inflammatory responses.

2.
Biol. Res ; 572024.
Article in English | LILACS-Express | LILACS | ID: biblio-1564037

ABSTRACT

Background Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. Results Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. Conclusions Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.

3.
Rev. argent. microbiol ; Rev. argent. microbiol;55(4): 4-4, Dec. 2023.
Article in English | LILACS-Express | LILACS | ID: biblio-1550711

ABSTRACT

Abstract Chromatin remodeling enzymes are important "writers'', "readers'' and "erasers'' of the epigenetic code. These proteins are responsible for the placement, recognition, and removal of molecular marks in histone tails that trigger structural and functional changes in chromatin. This is also the case for histone deacetylases (HDACs), i.e., enzymes that remove acetyl groups from histone tails, signaling heterochromatin formation. Chromatin remodeling is necessary for cell differentiation processes in eukaryotes, and fungal pathogenesis in plants includes many adaptations to cause disease. Macrophomina phaseolina (Tassi) Goid. is a nonspe-cific, necrotrophic ascomycete phytopathogen that causes charcoal root disease. M. phaseolina is a frequent and highly destructive pathogen in crops such as common beans (Phaseolus vulgaris L.), particularly under both water and high temperature stresses. Here, we evaluated the effects of the classical HDAC inhibitor trichostatin A (TSA) on M. phaseolina in vitro growth and virulence. During inhibition assays, the growth of M. phaseolina in solid media, as well as the size of the microsclerotia, were reduced (p <0.05), and the colony morphology was remark-ably affected. Under greenhouse experiments, treatment with TSA reduced (p <0.05) fungal virulence in common bean cv. BAT 477. Tests of LIPK, MAC1 and PMK1 gene expression during the interaction of fungi with BAT 477 revealed noticeable deregulation. Our results provide additional evidence about the role of HATs and HDACs in important biological processes of M. phaseolina.


Resumen Las enzimas remodeladoras de la cromatina son «escritores¼, «lectores¼ y «borradores¼ importantes del código epigenético. Estas proteínas son responsables de la localización, el reconocimiento y la remoción de las marcas moleculares sobre las terminaciones de las histonas que desencadenan cambios funcionales y estructurales en la cromatina. Es el caso de las desacetilasas de histonas (HDAC), enzimas que remueven grupos acetilo de las «colas¼ de las histonas, señalizando la formación de heterocromatina. La anterior es una actividad necesaria en los procesos de diferenciación celular de los eucariotas, y se conoce que la patogénesis fúngica en las plantas requiere de adaptaciones diversas para ocasionar enfermedad. Macrophomina phaseolina (Tassi) Goid. es un ascomiceto fitopatógeno, necrótrofo e inespecífico, causante de la pudrición carbonosa. Este es un hongo frecuente y altamente destructivo en cultivos como fríjol común (Phaseolus vulgaris L.), particularmente bajo estrés hídrico y térmico. En este trabajo evaluamos los efectos del inhibidor de HDAC clásicas tricostatina A (TSA) sobre el crecimiento in vitro y la virulencia de M. phaseolina. El TSA redujo el crecimiento de M. phaseolina en medio sólido y el tamano de los microesclerocios (p < 0,05), lo que afectó la morfología colonial. En invernadero, el tratamiento con TSA disminuyó (p<0,05) la gravedad de la infección en la variedad de frijol BAT 477. La expresión de los genes de patogenicidad LIPK, MAC1 y PMK1 durante la interacción del hongo con la planta reveló una desregulación importante. Estos resultados proporcionan evidencia adicional del papel que cumplen las HDAC en la regulación de procesos biológicos fundamentales de M. phaseolina. © 2023 Asociación Argentina de Microbiología. Publicado por Elsevier Espana, S.L.U.

4.
Rev. obstet. ginecol. Venezuela ; 83(3): 270-280, jul. 2023. ilus, tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1573192

ABSTRACT

Objetivo: Verificar que los recolectores de orina no son tóxicos para los espermatozoides. Métodos: Se evaluó la toxicidad de recipientes de material de vidrio (control) y plástico (recolector de orina) con muestras de semen de buena concentración y movilidad de espermatozoides, mediante el estudio de la movilidad espermática a intervalos de 1 hora, a temperatura ambiente, durante 4 horas, siguiendo lineamientos de la quinta edición del Manual de la Organización Mundial de la Salud para el procesamiento de muestras de semen. Se comparó la movilidad progresiva entre ambos tipos de recipientes (vidrio y plástico) y se evaluaron las características morfotintoriales de los espermatozoides con la tinción diferencial de fluorescencia modificada. Resultados: No se hallaron diferencias estadísticamente significativas (p = 0,334) entre los grupos. Los espermatozoides que emitieron una fluorescencia verde, se categorizaron como normales y presentaron una fuerte correlación (r = 1,000; p = 0,000); mientras que, las tinciones amarilla (r = -0,838, p = 0,009) y anaranjada (r = 0,940, p = 0,000), estuvieron altamente correlacionadas con anormalidades de los espermatozoides, destacándose que la fluorescencia anaranjada, tuvo una alta correlación (r = 0,940, p = 0,000) con anormalidades de la cabeza. Conclusión: El recolector de plástico no tiene efectos tóxicos sobre los espermatozoides, satisface las necesidades de recogida de la muestra de semen. Con la tinción diferencial de fluorescencia modificada, la tinción verde se asocia a espermatozoides morfológicamente normales y las amarilla y anaranjada se asocian a anormalidades de la cabeza, pieza intermedia y pieza principal de los espermatozoides(AU)


Objective: To verify that urine collectors are not toxic to sperm. Methods: The toxicity of glass (control) and plastic (urine collector) containers with semen samples of good concentration and sperm motility was evaluated by studying sperm motility at intervals of 1 hour, at room temperature, for 4 hours, following guidelines of the fifth edition of the World Health Organization Manual for the processing of semen samples. The progressive motility between both types of containers (glass and plastic) was compared and the morphotintorial characteristics of the spermatozoa were evaluated with the modified fluorescence differential stain. Results: No statistically significant differences (p = 0.334) were found between the groups. Spermatozoa that emitted a green fluorescence were categorized as normal and presented a strong correlation (r = 1,000; p = 0.000); Whereas, yellow (r = -0.838, p = 0.009) and orange (r = 0.940, p = 0.000) stains were highly correlated with sperm abnormalities, highlighting that orange fluorescence had a high correlation (r = 0.940, p = 0.000) with head abnormalities. Conclusion: The plastic collector has no toxic effects on sperm, it satisfies the needs of collection of the semen sample. With modified fluorescence differential staining, green staining is associated with morphologically normal spermatozoa and yellow and orange stains are associated with abnormalities of the head, middle piece, and main piece of sperm(AU)


Subject(s)
Humans , Male , Adolescent , Adult , Middle Aged , Plastics , Toxic Substances , Urine Specimen Collection , Seminal Proteins , Infertility , Spermatozoa , Staining and Labeling , Toxicity , Fluorescence
5.
Asian j. androl ; Asian j. androl;(6): 158-165, 2023.
Article in English | WPRIM | ID: wpr-971028

ABSTRACT

Prostate cancer is one of the most common diseases in men worldwide. Surgery, radiation therapy, and hormonal therapy are effective treatments for early-stage prostate cancer. However, the development of castration-resistant prostate cancer has increased the mortality rate of prostate cancer. To develop novel drugs for castration-resistant prostate cancer, the molecular mechanisms of prostate cancer progression must be elucidated. Among the signaling pathways regulating prostate cancer development, recent studies have revealed the importance of noncanonical wingless-type MMTV integration site family (WNT) signaling pathways, mainly that involving WNT5A, in prostate cancer progression and metastasis; however, its role remains controversial. Moreover, chromatin remodelers such as the switch/sucrose nonfermentable (SWI/SNF) complex and chromodomain helicase DNA-binding proteins 1 also play important roles in prostate cancer progression through genome-wide gene expression changes. Here, we review the roles of noncanonical WNT signaling pathways, chromatin remodelers, and epigenetic enzymes in the development and progression of prostate cancer.


Subject(s)
Male , Humans , Wnt Signaling Pathway , Chromatin , Prostatic Neoplasms, Castration-Resistant , Chromatin Assembly and Disassembly
6.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;56: e12922, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1520463

ABSTRACT

Nuclear proliferation marker MIB-1 (Ki-67) immunohistochemistry (IHC) is used to examine tumor cell proliferation. However, the diagnostic or prognostic value of the Ki-67 nuclear staining intensity and location, defined as nuclear gradient (NG), has not been assessed. This study examined the potential association between Ki-67 NG and cell cycle phases and its effect on the prognosis of pulmonary typical carcinoid (PTC) tumors. We propose a method for classifying the NG of Ki-67 during the cell cycle and compare the results between PTC, pulmonary adenocarcinoma (PAD), and breast ductal carcinoma (BDC). A literature review and objective analysis of IHC-stained paraffin sections were used to determine the Ki-67 labeling index and composed a stratification of the NG into NG1, NG2, and NG3/4 categories. A semi-automated image analysis protocol was established to determine the Ki-67 NG in PTC, PAD, and BDC. High intraobserver consistency and moderate interobserver agreement were achieved in the determination of Ki-67 NG in tumor specimens. NG1 and NG2 were lower in PTC than in PAD and BDC. Cox multivariate analysis of PTC after adjusting for age and number of metastatic lymph nodes showed that Ki-67 NG1 and NG2 significantly predicted clinical outcomes. The semi-automated method for quantification of Ki-67 nuclear immunostaining proposed in this study could become a valuable diagnostic and prognostic tool in PTC.

7.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;56: e12854, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1520474

ABSTRACT

During the tumorigenic process, cancer cells may become overly dependent on the activity of backup cellular pathways for their survival, representing vulnerabilities that could be exploited as therapeutic targets. Certain molecular vulnerabilities manifest as a synthetic lethality relationship, and the identification and characterization of new synthetic lethal interactions may pave the way for the development of new therapeutic approaches for human cancer. Our goal was to investigate a possible synthetic lethal interaction between a member of the Chromodomain Helicase DNA binding proteins family (CHD4) and a member of the histone methyltransferases family (SETDB1) in the molecular context of a cell line (Hs578T) representing the triple negative breast cancer (TNBC), a subtype of breast cancer lacking validated molecular targets for treatment. Therefore, we employed the CRISPR-Cas9 gene editing tool to individually or simultaneously introduce indels in the genomic loci corresponding to the catalytic domains of SETDB1 and CHD4 in the Hs578T cell line. Our main findings included: a) introduction of indels in exon 22 of SETDB1 sensitized Hs578T to the action of the genotoxic chemotherapy doxorubicin; b) by sequentially introducing indels in exon 22 of SETDB1 and exon 23 of CHD4 and tracking the percentage of the remaining wild-type sequences in the mixed cell populations generated, we obtained evidence of the existence of a synthetic lethality interaction between these genes. Considering the lack of molecular targets in TNBC, our findings provided valuable insights for development of new therapeutic approaches not only for TNBC but also for other cancer types.

8.
Chinese Journal of Dermatology ; (12): 724-736, 2023.
Article in Chinese | WPRIM | ID: wpr-1028826

ABSTRACT

Objective:To determine the expression of Brahma-related gene 1 (BRG1) in cutaneous squamous cell carcinoma (cSCC) tissues and cells, and to investigate molecular mechanisms underlying the regulatory effect of its interaction with activating transcription factor 2 (ATF2) on the proliferation, migration and invasion of cSCC cells.Methods:From 2015 to 2021, 66 paraffin-embedded actinic keratosis (AK) tissue samples and 80 paraffin-embedded cSCC (including squamous cell carcinoma in situ) tissue samples were collected from the Department of Dermatology, Affiliated Hospital 2 of Nantong University, and the diagnoses of all the cases were confirmed histopathologically; at the same time, 35 paraffin-embedded normal skin tissue samples obtained by cosmetic surgery served as normal control group. Immunohistochemical staining was performed to determine the BRG1 expression in cSCC, AK, and normal skin tissues, and correlations between BRG1 expression and clinicopathological parameters of cSCC patients were analyzed. Fresh tissue samples were collected from 12 cSCC patients and 12 healthy controls, and cSCC cell lines A431 and Scl-1 and a human immortalized keratinocyte cell line HaCaT were routinely cultured; real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to determine the mRNA expression of BRG1 in tissues and cells, and co-immunoprecipitation assay and cellular immunofluorescence staining were conducted to analyze the interaction between BRG1 and ATF2. The expression of BRG1 (BRG1 siRNA1 - 5 groups) and ATF2 (ATF2-shRNA group) in A431 and Scl-1 cells was knocked down by RNA interference, and cells transfected with negative control siRNA or shNC served as controls (control siRNA group and shNC group, respectively), cell counting kit-8 (CCK8) assay, colony formation assay, cell scratch assay, and Transwell assay were conducted to evaluate effects of knocking down BRG1 and ATF2 on the proliferation, migration, and invasion of cSCC cells. Comparisons of measurement data among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were conducted using Dunnett- t test. Results:Immunohistochemical staining showed that the expression intensity of BRG1 protein was significantly lower in the cSCC and AK tissues than in the normal skin tissues ( χ2 = 44.40, P < 0.001). qRT-PCR showed that the mRNA expression level of BRG1 was significantly lower in the cSCC tissues (1.345 ± 0.956) than in the normal skin tissues (2.499 ± 1.501, t = 2.25, P = 0.035), and also significantly lower in A431 and Scl-1 cells (0.041 ± 0.002, 0.026 ± 0.003, respectively) than in HaCaT cells (0.135 ± 0.033, t = 4.95, 5.73, P = 0.008, 0.005, respectively). The low expression of BRG1 was associated with tumors at sun-exposed sites ( P = 0.041), low tumor differentiation ( P = 0.001), and high Broder′s grade ( P < 0.001) in the cSCC patients. In both A431 cells and Scl-1 cells, the BRG1 siRNA1 group and BRG1 siRNA2 group showed significantly increased numbers of cell colonies, migratory cells and invasive cells, as well as cell migration rates compared with the control siRNA group (all P < 0.05). Co-immunoprecipitation assay showed that BRG1 protein could bind to ATF2 protein in A431 and Scl-1 cells, and immunofluorescence staining showed that the two proteins were co-localized; compared with the control siRNA group, the BRG1 siRNA1 group (both A431 and Scl-1 cells) and BRG1 siRNA2 group (A431 cells) both showed increased phosphorylation and activation of ATF2 (all P < 0.05) ; in both A431 cells and Scl-1 cells, the shATF2 group showed significantly decreased numbers of cell colonies (both P = 0.001), cellular proliferative activity at 24 - 96 hours (all P < 0.001), and numbers of migratory cells and invasive cells compared with the shNC group (all P ≤ 0.001) . Conclusion:BRG1 was lowly expressed in the cSCC and AK tissues, and could inhibit the proliferation, migration, and invasion of cSCC cells; ATF2 could promote the proliferation, migration, and invasion of cSCC cells; BRG1 may exert an anti-tumor effect by interacting with ATF2 protein and inhibiting phosphorylation-dependent activation of ATF2.

9.
Acta Pharmaceutica Sinica B ; (6): 2234-2249, 2023.
Article in English | WPRIM | ID: wpr-982848

ABSTRACT

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

10.
Article in Chinese | WPRIM | ID: wpr-1015647

ABSTRACT

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

11.
Protein & Cell ; (12): 683-697, 2023.
Article in English | WPRIM | ID: wpr-1010771

ABSTRACT

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.


Subject(s)
Animals , Mice , Methylation , Chromatin , Histones/metabolism , RNA, Messenger/genetics , Methyltransferases/metabolism , RNA/metabolism
12.
Neuroscience Bulletin ; (6): 1087-1104, 2023.
Article in English | WPRIM | ID: wpr-982458

ABSTRACT

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.


Subject(s)
Mice , Animals , Memory , Chromatin Assembly and Disassembly , Hippocampus/metabolism , Transcription Factors/metabolism , Chromatin/metabolism , Metabolic Networks and Pathways
13.
J. biomed. eng ; Sheng wu yi xue gong cheng xue za zhi;(6): 617-624, 2023.
Article in Chinese | WPRIM | ID: wpr-1008880

ABSTRACT

As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.


Subject(s)
Cell Nucleus , Biophysics , Cytoskeleton , Phenotype , Signal Transduction
14.
Protein & Cell ; (12): 258-280, 2022.
Article in English | WPRIM | ID: wpr-929157

ABSTRACT

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.


Subject(s)
Humans , Chromatin , Chromosomes , Genome , Lamin Type B/genetics
15.
Acta Pharmaceutica Sinica B ; (6): 1225-1239, 2022.
Article in English | WPRIM | ID: wpr-929366

ABSTRACT

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

16.
Article in Chinese | WPRIM | ID: wpr-958250

ABSTRACT

The high diversity of T cell receptors (TCRs) is the basis for recognizing antigens, playing an essential role in adaptive immunity. TCR diversity is generated from V(D)J rearrangement during the thymocyte development in the thymus. Standing out from the four TCR genes, Tcra and Tcrd genes are characterized by locating at the same locus and sharing specific V genes. Hence, their rearrangement and regulation have a certain particularity. Previous studies mainly focused on cis-regulatory elements and trans-acting factors regulating the Tcra/ Tcrd rearrangement. However, recent progress has shown that chromatin spatial organization plays an essential role in antigen receptor gene rearrangement. Chromatin organization proteins, such as CTCF-Cohesin, are involved in regulating rearrangement and enhancing the diversity of TCR repertoire by loop extrusion. Recombinase RAG also scans chromatin of antigen receptor genes for rearrangement. This review described the progress in the rearrangement of Tcra and Tcrd genes and the possible regulatory mechanism, especially the influence of the chromatin spatial organization.

17.
Braz. j. biol ; 82: e253898, 2022. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1360194

ABSTRACT

High temperature stress events are critical factors inhibiting crop yield. Meanwhile, world population is growing very rapidly and will be reached up to 9 billion by 2050. To feed increasing world population, it is challenging task to increase about 70% global food productions. Food crops have significant contribution toward global food demand and food security. However, consequences from increasing heat stress events are demolishing their abilities to survive and sustain yield when subjected to extreme high temperature stress. Therefore, there is dire need to better understand response and tolerance mechanism of food crops following exposure to heat stress. Here, we aimed to provide recent update on impact of high temperature stress on crop yield of food crops, pollination, pollinators, and novel strategies for improving tolerance of food crop under high temperature stress. Importantly, development of heat-resistant transgenic food crops can grant food security through transformation of superior genes into current germplasm, which are associated with various signaling pathways as well as epigenetic regulation in response to extreme high temperature stress.


Eventos de estresse de alta temperatura são fatores críticos que inibem o rendimento das culturas. Enquanto isso, a população mundial está crescendo muito rapidamente e atingirá até 9 bilhões em 2050. Para alimentar a crescente população mundial, é uma tarefa desafiadora aumentar cerca de 70% da produção global de alimentos. As culturas alimentares têm uma contribuição significativa para a procura global de alimentos e a segurança alimentar. No entanto, as consequências do aumento de eventos de estresse por calor estão destruindo suas habilidades de sobreviver e manter a produção quando submetidos a estresse de alta temperatura. Portanto, há uma necessidade urgente de entender melhor o mecanismo de resposta e tolerância das safras de alimentos após a exposição ao estresse por calor. Aqui, nosso objetivo foi fornecer atualizações recentes sobre o impacto do estresse de alta temperatura no rendimento de culturas de alimentos, polinização, polinizadores e novas estratégias para melhorar a tolerância de culturas de alimentos sob estresse de alta temperatura. É importante ressaltar que o desenvolvimento de culturas alimentares transgênicas resistentes ao calor pode garantir segurança alimentar por meio da transformação de genes superiores em germoplasma atual, que estão associados a várias vias de sinalização, bem como à regulação epigenética em resposta ao estresse de alta temperatura extrema.


Subject(s)
Food Demand , Heat Stress Disorders , Food, Genetically Modified , Agriculture , Pollination , Food , Food Supply
18.
Braz. j. biol ; 822022.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468796

ABSTRACT

Abstract High temperature stress events are critical factors inhibiting crop yield. Meanwhile, world population is growing very rapidly and will be reached up to 9 billion by 2050. To feed increasing world population, it is challenging task to increase about 70% global food productions. Food crops have significant contribution toward global food demand and food security. However, consequences from increasing heat stress events are demolishing their abilities to survive and sustain yield when subjected to extreme high temperature stress. Therefore, there is dire need to better understand response and tolerance mechanism of food crops following exposure to heat stress. Here, we aimed to provide recent update on impact of high temperature stress on crop yield of food crops, pollination, pollinators, and novel strategies for improving tolerance of food crop under high temperature stress. Importantly, development of heat-resistant transgenic food crops can grant food security through transformation of superior genes into current germplasm, which are associated with various signaling pathways as well as epigenetic regulation in response to extreme high temperature stress.


Resumo Eventos de estresse de alta temperatura são fatores críticos que inibem o rendimento das culturas. Enquanto isso, a população mundial está crescendo muito rapidamente e atingirá até 9 bilhões em 2050. Para alimentar a crescente população mundial, é uma tarefa desafiadora aumentar cerca de 70% da produção global de alimentos. As culturas alimentares têm uma contribuição significativa para a procura global de alimentos e a segurança alimentar. No entanto, as consequências do aumento de eventos de estresse por calor estão destruindo suas habilidades de sobreviver e manter a produção quando submetidos a estresse de alta temperatura. Portanto, há uma necessidade urgente de entender melhor o mecanismo de resposta e tolerância das safras de alimentos após a exposição ao estresse por calor. Aqui, nosso objetivo foi fornecer atualizações recentes sobre o impacto do estresse de alta temperatura no rendimento de culturas de alimentos, polinização, polinizadores e novas estratégias para melhorar a tolerância de culturas de alimentos sob estresse de alta temperatura. É importante ressaltar que o desenvolvimento de culturas alimentares transgênicas resistentes ao calor pode garantir segurança alimentar por meio da transformação de genes superiores em germoplasma atual, que estão associados a várias vias de sinalização, bem como à regulação epigenética em resposta ao estresse de alta temperatura extrema.

19.
Article in Chinese | WPRIM | ID: wpr-1015795

ABSTRACT

Chromatin accessibility is one of the important indicators to evaluate the stability of chromatin structure, which is used to evaluate the binding ability of chromatin binding factors to chromosome DNA. It plays an important role in different nuclear processes, including gene transcription regulation and DNA damage repair. Abnormal regulation of chromatin accessibility is closely related to the occurrence and development of a variety of diseases, including tumors and neurodegenerative diseases. Therefore, exploration of this attribute has become a hot spot in the field of life science and disease. More and more new technologies came into being, such as chromatin conformation capture, high-throughput sequencing, and the combination of these two technologies. With the progress of technology, more and more factors involved in the regulation of chromosome accessibility have been found and summarized, including nucleosome occupation, histone modification and non-coding RNA. A number of large-scale genomic data have drawn the chromatin accessibility map of a variety of diseases, which provides data support for revealing the relationship between the occurrence and development of diseases and chromatin accessibility. Meanwhile, with the development of single-cell chromatin accessibility sequencing technology, the investigation for division of cell types at chromatin level was achieved, which makes up for the deficiency of solely relying on gene expression for cell type division. This review will explain the development and prospect of the research about chromatin accessibility from the aspects of chromatin composition and accessibility, factors affecting chromatin accessibility, detection methods of chromatin accessibility, and its roles in cancer, briefly.

20.
Rev. colomb. cienc. pecu ; 34(2): 126-144, Apr.-June 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394936

ABSTRACT

Abstract Background: The results from automated equipment and peripheral blood smears allow correlating clinical data with cellular blood counts (CBC), generating information on pathologies of hematological and non-hematological origin in dogs. Objective: To describe qualitative and quantitative magnitudes of CBC in healthy donor dogs of a blood- bank in Medellín (Colombia). Methods: A descriptive-prospective study was carried out from 146 records of CBC results from a blood-bank. The samples were processed by automated equipment, and trained personnel performed the observation of peripheral blood smears to collect qualitative information. Variables such as age, sex, breed, quantitative results, and observations of the peripheral blood smears were considered. For the definition of biological intervals (BIs), the mean and two standard deviations were used for the data with a normal distribution. Otherwise, the 2.5th and 97.5th percentiles were used. Results: The size, granularity, and cytoplasmic vacuoles in monocytes and polymorphonuclear eosinophils, as well as the presence of Barr chromatin and occasional circulating erythroblasts, were remarkable findings to the peripheral blood smear. With the standardization of data obtained from dogs of large and giant breeds, the present work provides BIs for some of the CBC data in the studied population. Conclusion: The findings of the present study allow approximations to the definition of alterations in blood cells and their counts, which can guide the veterinarian towards an early diagnosis in dogs.


Resumen Antecedentes: Los datos obtenidos de equipos automatizados y extendidos de sangre periférica permiten correlacionar la clínica y los resultados del hemograma, generando información de interés sobre patologías de origen hematológico y no hematológico en perros. Objetivo: Describir las magnitudes cualitativas y cuantitativas del hemograma en perros sanos, donantes de un banco de sangre en Medellín (Colombia). Métodos: Se realizó un estudio descriptivo-prospectivo a partir de 146 registros de resultados de hemograma remitidos por un banco de sangre. Las muestras fueron procesadas por un equipo automatizado y personal entrenado realizó la observación del extendido de sangre periférica para la colección de información de corte cualitativo. Variables como edad, sexo, raza, resultados cuantitativos de las muestras y observaciones al extendido de sangre periférica fueron consideradas. Para la definición de intervalos biológicos (IBs) se utilizaron la media y dos desviaciones estándar para los datos con distribución normal. De lo contrario, se utilizaron los percentiles 2,5 y 97,5. Resultados: El tamaño, granularidad y vacuolas citoplasmáticas en monocitos y polimorfonucleares eosinófilos, así como la presencia de Cromatina de Barr y eritroblastos circulantes ocasionales fueron hallazgos llamativos al extendido de sangre periférica. Con la normalización de los datos para caninos de razas grandes y gigantes, el presente trabajo aporta IBs para algunos de los datos del hemograma en la población estudiada. Conclusión: Los hallazgos del presente estudio permiten aproximaciones a la definición de alteraciones en las células hemáticas y sus conteos, que pueden orientar al médico veterinario hacia un diagnóstico temprano en perros.


Resumo Antecedentes: As informações obtidas de equipamentos automatizados e esfregaços de sangue periférico permitem correlacionar os resultados clínicos e de hemogramas, gerando informações interessantes sobre patologias de origem hematológica e não hematológica em cães. Objetivo: Descrever as magnitudes qualitativa e quantitativa do hemograma em cães saudáveis, doadores de um banco de sangue em Medellín (Colômbia). Métodos: Foi realizado um estudo descritivo-prospectivo a partir de 146 registros de resultados de hemograma encaminhados por um banco de sangue. As amostras foram processadas por uma equipe automatizada e pessoal treinado observou o esfregaço de sangue periférico para a coleta de informações qualitativas. Foram consideradas variáveis como idade, sexo, raça, resultados quantitativos das amostras e observações do esfregaço de sangue periférico. Para a definição de intervalos biológicos (IBs), foram utilizados a média e dois desvios-padrão para os dados com distribuição normal. Caso contrário, foram utilizados os percentis 2,5 e 97,5. Resultados: O tamanho, a granularidade e os vacúolos citoplasmáticos dos monócitos e das células polimorfonucleares dos eosinófilos, bem como a presença da cromatina de Barr e ocasionais eritroblastos circulantes foram achados marcantes na disseminação do sangue periférico. Com a normalização dos dados para cães de raças grandes e gigantes, o presente trabalho fornece IBs para alguns dos dados de hemograma na população estudada. Conclusão: Os achados do presente estudo permitem aproximações à definição de alterações nas células sanguíneas e suas contagens, o que pode orientar o médico veterinário responsável pelo diagnóstico precoce em cães.

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