Effects of Chemical inhibition of histone deacetylase proteins in the growth and virulence of Macrophomina phaseolina (Tassi) Goid / Efectos de la inhibición química de las proteínas desacetilasas de histonas en el crecimiento y la virulencia de Macrophomina phaseolina (Tassi) Goid

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.

Recent advances in prostate cancer: WNT signaling, chromatin regulation, and transcriptional coregulators / 亚洲男科学杂志(英文版)

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.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins

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.

Chromatin Remodeling Factor SMARCA5 is Essential for Hippocampal Memory Maintenance via Metabolic Pathways in Mice / 神经科学通报·英文版

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.

A semi-automated microscopic image analysis method for scoring Ki-67 nuclear immunostaining

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.

Evidence of a synthetic lethality interaction between SETDB1 histone methyltransferase and CHD4 chromatin remodeling protein in a triple negative breast cancer cell line

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.

Response and tolerance mechanism of food crops under high temperature stress: a review / Mecanismo de resposta e tolerância de culturas alimentares sob estresse de alta temperatura: uma revisão

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.

Response and tolerance mechanism of food crops under high temperature stress: a review

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.

WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit

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.

Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

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.

Rearrangement of T cell receptor genes Tcra and Tcrd and its regulatory mechanism / 中华微生物学和免疫学杂志

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.

Estimating biological reference intervals for cell blood counts in a dog population / Estimación de los intervalos biológicos de referencia para conteos celulares sanguíneos en una población de perros / Estimando intervalos de referência biológica para contagens de células sanguíneas em uma população de cães

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.

SMYD3-PARP16 axis accelerates unfolded protein response and mediates neointima formation

Neointimal hyperplasia after vascular injury is a representative complication of restenosis. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) is involved in the pathogenesis of vascular intimal hyperplasia. PARP16, a member of the poly(ADP-ribose) polymerases family, is correlated with the nuclear envelope and the ER. Here, we found that PERK and IRE1

3D chromatin architecture and epigenetic regulation in cancer stem cells

Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.

3D organization profiling of human hepatocellular carcinoma cell line PLC/PRF/5 in comparison with normal human liver cell line L02 by in situ Hi-C / 生物工程学报

Genetic and epigenetic alterations accumulate in the process of hepatocellular carcinogenesis, but the role of genomic spatial organization in HCC is still unknown. Here, we performed in situ Hi-C in HCC cell line PLC/PRF/5 compared with normal liver cell line L02, together with RNA-seq and ChIP-seq of SMC3/CTCF/H3K27ac. The results indicate that there were significant compartment switching, TAD shifting and loop pattern altering in PLC/PRF/5. These spatial changes are correlated with abnormal gene expression and more opening promoter regions of the HCC cell line. Thus, the 3D genome organization alterations in PLC/PRF/5 are important in epigenetic mechanisms of HCC tumorigenesis.

Effect of interactions of chromatin regulatory elements with different promoters on the regulation of gene expression / 生物工程学报

The effect of altering the promoter region of ubiquitous chromatin-opening element (UCOE) and matrix attachment region (MAR) on stable and efficient expression of genes was investigated. Four different promoters were tested, namely, oct4 containing an enhancer region, sox2 having a CpG island, nanog having no regulatory elements, and CMV containing a CpG island and an enhancer region. Eight reporter plasmids were constructed: pOCT4-UCOE, pOCT4-MAR, pSOX2-UCOE, pSOX2-MAR, pNANOG-UCOE, pNANOG-MAR, pCMV-UCOE, and pCMV-MAR. Stable and efficient expression was observed when UCOE combined with the oct4 promoter, whereas the sox2 was the best promoter suited for MAR. Comparison of the stable clones of oct4-UCOE and sox2-MAR showed that UCOE-regulated expression is more stable and efficient than MAR-regulated expression. When CpG island-containing promoter is linked with UCOE, stable and efficient expression could be observed. These data suggest that an enhancer region in the promoter leads to high, yet unstable expression when combined with UCOE, whereas CpG islands stabilize expression. In conclusion, UCOE and MAR interact with regulatory elements on the promoter by altering the chromatin open state and chromatin loop to regulate gene expression.

Non-coding RNAs and chromatin: key epigenetic factors from spermatogenesis to transgenerational inheritance

Cellular fate and gene expression patterns are modulated by different epigenetic factors including non-coding RNAs (ncRNAs) and chromatin organization. Both factors are dynamic throughout male germ cell differentiation on the seminiferous tubule, despite the transcriptional inactivation in the last stages of spermatogenesis. Sperm maturation during the caput-to-cauda transit on the epididymis involves changes in chromatin organization and the soma-to-germ line transference of ncRNAs that are essential to obtain a functional sperm for fertilization and embryo development. Here, the male environment (diseases, drugs, mental stress) is crucial to modulate these epigenetic factors throughout sperm maturation, affecting the corresponding offspring. Paternal transgenerational inheritance has been directly related to sperm epigenetic changes, most of them associated with variations in the ncRNA content and chromatin marks. Our aim is to give an overview about how epigenetics, focused on ncRNAs and chromatin, is pivotal to understand spermatogenesis and sperm maturation, and how the male environment impacts the sperm epigenome modulating the offspring gene expression pattern.

Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders

Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists ofmethylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation.PTMs have fundamental roles in chromatin structure and function. Histone modifications have also beenknown as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expressionby altering chromatin structure. Histone modifications act in varied biological processes such as transcriptionalactivation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defectsin the PTMs pathway have been associated with the occurrence and progression of various human diseases,such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson’sdisease, Alzheimer’s disease, and Huntington’s disease. Histone modifications are reversible and used aspotential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancercells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications andhave examined the role of these modifications in the development of cancer.

La densidad óptica nuclear como indicador diagnóstico en el carcinoma papilar de tiroides / Nuclear optical density as a diagnostic indicator in papillary thyroid carcinoma

Introducción: El carcinoma papilar de tiroides es la causa más frecuente de cáncer de naturaleza endocrina. Constituye la variante histológica de mejor pronóstico, sin embargo, en ocasiones es motivo de importantes dudas diagnósticas con otras variantes de evolución tórpida, lo que dificulta que un mayor número de pacientes se beneficie con un tratamiento individualizado y conservador. Por esta razón, se desarrollan estudios en los que cada vez más se añaden procedimientos morfométricos y densitométricos, los que permiten disminuir la subjetividad en el diagnóstico histopatológico. Objetivo: Determinar la densidad óptica nuclear en el carcinoma papilar de tiroides. Método: Se realizó un estudio morfométrico de serie de casos con 12 pacientes con carcinoma papilar de tiroides, atendidos en el Hospital Provincial Universitario Vladimir Ilich Lenin. Se seleccionaron 36 campos y se midieron 965 núcleos celulares, lo que constituyó la muestra del estudio. Se determinó la densidad óptica nuclear como indicador morfométrico del carcinoma papilar de tiroides. Resultados: El valor de la densidad óptica nuclear fue 1,14, considerado bajo. Conclusiones: Se determinó la densidad óptica nuclear del carcinoma papilar de tiroides en los casos estudiados, lo que puede contribuir a su diagnóstico histopatológico(AU)

Background: Papillary thyroid carcinoma is the most frequent cause of endocrine cancer. It is an histological variant with the best prognosis, however, sometimes it is a reason for significant diagnostic doubts with other variants of torpid evolution, which makes it difficult for a greater number of patients to benefit from an individualized and conservative treatment. For this reason, studies are developed in which more and more morphometric and densitometric procedures are added, which allow reducing the subjectivity in the histopathological diagnosis and could represent a tool of great value. Objective: To determine the nuclear optical density in papillary thyroid carcinoma. Method: A morphometric study of a series of cases was carried out with 12 patients with this histopathological diagnosis, attended at the Vladimir Ilich Lenin University Provincial Hospital. We chose 36 fields and 965 cell nuclei were measured, which constituted the study sample. Nuclear optical density was determined as a morphometric indicator of papillary thyroid carcinoma. Results: The value of nuclear optical density was 1, 14. It is considered low. Conclusion: Nuclear optical density of papillary thyroid carcinoma was determined in the studied cases that may contribute to histopathological diagnosis(AU)

Elucidation and genetic intervention of CO2 concentration mechanism in Chlamydomonas reinhardtii for increased plant primary productivity

Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists ofmethylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation.PTMs have fundamental roles in chromatin structure and function. Histone modifications have also beenknown as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expressionby altering chromatin structure. Histone modifications act in varied biological processes such as transcriptionalactivation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defectsin the PTMs pathway have been associated with the occurrence and progression of various human diseases,such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson’sdisease, Alzheimer’s disease, and Huntington’s disease. Histone modifications are reversible and used aspotential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancercells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications andhave examined the role of these modifications in the development of cancer.