Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 386
Filter
1.
Chinese Journal of Biotechnology ; (12): 4102-4110, 2021.
Article in Chinese | WPRIM | ID: wpr-921491

ABSTRACT

The abundance of proteins in human urine is low and easily to be masked by high-abundance proteins during mass spectrometry analysis. Development of efficient and highly selective enrichment methods is therefore a prerequisite for achieving deep coverage of urine protein markers. Notably, different experimental methods would affect the urine protein enrichment efficacy and the coverage of urine proteome. In this study, ultrafiltration, nitrocellulose membrane enrichment and saturated ammonium sulfate precipitation were used to process 10 mL urine samples from five healthy volunteers and five bladder cancer patients. The urine proteins were enriched and separate by SDS-PAGE to compare the purification efficiency of different methods. Moreover, the peptide identification effects of different purification methods were analyzed by mass spectrometry to determine the best method for enriching urine protein histones. Saturated ammonium sulfate precipitation method outperformed the ultrafiltration and the nitrocellulose membrane enrichment methods in terms of the protein enrichment efficacy and quality. The interference of highly abundant albumin was reduced, whereas the amount of low-abundance protein was increased, and the sensitivity of mass spectrometry identification was increased. The saturated ammonium sulfate precipitation method may be applied for large-scale urine processing for screening clinical diagnostic markers through proteomics.


Subject(s)
Histones , Humans , Mass Spectrometry , Proteome , Proteomics , Urinalysis
2.
Acta Physiologica Sinica ; (6): 980-990, 2021.
Article in Chinese | WPRIM | ID: wpr-921303

ABSTRACT

The normal development of follicles involves a series of complex life processes such as ordered transcriptional activation and inhibition, which is crucial for female reproductive ability. Histone methylation can change the chromatin state in cells and affect the transcription activity of genes. Current studies indicate that epigenetic modifications such as histone methylation play an important regulatory role in follicular development in female mammals. This paper summarized the relationship between H3K4, H3K9 methylation and germ cell development, their regulatory effects, including their dynamical changes during follicular development, and the progress of H3K4me3 and other histone methylation binding to promoter regions of different genes to regulate gene expression and thus affect germ cell epigenetic reprogramming, oocyte transcription, meiosis and other processes. This review will provide a reference for the study of mechanisms related to histone methylation modification and the development and maturation of gonadal parenchymal cells.


Subject(s)
Animals , DNA Methylation , Epigenesis, Genetic , Female , Histones , Mammals , Ovarian Follicle/growth & development , Protein Processing, Post-Translational
3.
Chinese Journal of Biotechnology ; (12): 2645-2657, 2021.
Article in Chinese | WPRIM | ID: wpr-887830

ABSTRACT

Lysine acetylation is one of the major post-translational modifications and plays critical roles in regulating gene expression and protein function. Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from the lysines of both histone and non-histone proteins. The RPD3 family is the most widely studied HDACs. This article summarizes the regulatory mechanisms of Arabidopsis RPD3 family in several growth and development processes, which provide a reference for studying the mechanisms of RPD3 family members in regulating plant development. Moreover, this review may provide ideas and clues for exploring the functions of other members of HDACs family.


Subject(s)
Arabidopsis/metabolism , Histone Deacetylases/metabolism , Histones , Plant Development/genetics
4.
Protein & Cell ; (12): 29-38, 2021.
Article in English | WPRIM | ID: wpr-880916

ABSTRACT

Prostate cancer is the most commonly diagnosed non-cutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.


Subject(s)
Amino Acid Sequence , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 3-alpha/metabolism , Histone Demethylases/metabolism , Histones/metabolism , Humans , Male , Mutation , Prostate/pathology , Prostatic Neoplasms/pathology , Protein Binding , Protein Processing, Post-Translational , Receptors, Androgen/metabolism , Signal Transduction , Transcription, Genetic
5.
Protein & Cell ; (12): 7-28, 2021.
Article in English | WPRIM | ID: wpr-880895

ABSTRACT

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.


Subject(s)
Animals , Chromatin Assembly and Disassembly , DNA Methylation , DNA Transposable Elements , Embryo, Mammalian , Embryonic Development/genetics , Epigenesis, Genetic , Epigenome , Female , Fertilization/physiology , Gene Expression Regulation, Developmental , Histone Code , Histones/metabolism , Male , Mice , Oocytes/metabolism , Spermatozoa/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-879490

ABSTRACT

With the in-depth exploration of all stages in early-stage embryos, in particular zygotic genome activation and first cell lineage differentiation, researchers have found that early embryonic epigenetics follows a strict pattern of temporal and spatial modification. Previous studies have determined the inhibitory effect of H3K9me3 and H3K27me3 on genomic expression, and found that they are involved in many core biological events in the genome such as chromatin reprogramming, genomic imprinting, maintenance of embryonic stem cell pluripotency and somatic cell nuclear transfer, though the detailed molecular mechanism has remained elusive. From the point of developmental biology and epigenetics, this article has expounded the research progress on the methylation of H3K9 and H3K27 histones in early-stage embryos, which may provide a clue for the complex mechanism of embryonic development and improvement of culture method for embryos in vitro.


Subject(s)
Chromatin , Embryonic Development , Epigenesis, Genetic , Female , Gene Expression Regulation, Developmental , Histones/metabolism , Humans , Methylation , Pregnancy
7.
Braz. j. med. biol. res ; 53(10): e9861, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132476

ABSTRACT

Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.


Subject(s)
Animals , Female , Pregnancy , Rats , Cognitive Dysfunction , Acetylation , Histones , Maze Learning , Brain-Derived Neurotrophic Factor , Sevoflurane , Hippocampus
8.
Rev. chil. nutr ; 46(6): 792-799, dic. 2019. graf
Article in Spanish | LILACS | ID: biblio-1058143

ABSTRACT

RESUMEN La obesidad es una enfermedad multifactorial definida como acumulación patológica de grasa. Su prevalencia ha aumentado enormemente en el mundo. Chile presenta una de las mayores prevalencias de obesidad de la OCDE. Su casuística simplificada comprende una diferencia sostenida entre gasto e ingesta de energía, manteniendo un delta positivo traducido en mayor acumulación de grasa. No obstante, la etiología completa de esta enfermedad comprende también factores psicológicos, genéticos, ambientales, etc. El ambiente juega un papel clave en la predisposición al consumo de alimentos, a la realización de ejercicio físico, incluso afectando la susceptibilidad genómica, exacerbando o disminuyendo la carga genética. Esta modificación de susceptibilidad genética por el ambiente se conoce como epigenética, que se refiere a una serie de modificaciones por "sobre" la genética que son altamente modificables por factores ambientales. Se ha descrito que algunas de estas modificaciones pueden heredarse de una generación a otra, lo que otorga otro nivel de complejidad al estudio de nuevas terapias complementarias para frenar la tendencia al sobrepeso. En la presente revisión se describe cuales son las modificaciones epigenéticas más frecuentes encontradas, su relación con obesidad y dieta, y finalmente como se relaciona con la transmisión transgeneracional de esta patología.


ABSTRACT Obesity is a multifactorial disease defined by a pathological accumulation of body fat. Its prevalence has increased greatly across the world. Chile has one of the highest prevalence of obesity among OCDE countries. It is caused by a sustained difference between energy expenditure and intake, keeping a positive delta, which drives fat accumulation. However, its etiology is comprised several factors: psychological, genetics, environmental, etc. The environment plays a key role in the predisposition towards food consumption, the adoption of exercise, and genetic susceptibility, increasing or decreasing the genetic load towards obesity. This modification of susceptibility is known as epigenetics, which refers to modifications "over" genetics, which are highly modifiable by environmental factors. Some of these modifications can be inherited from one generation to another, granting a higher complexity level regarding designing novel complementary therapies against obesity. Thus, the present review described which epigenetic modifications are related to obesity and different dietary patterns, and finally how epigenetic modifications can be related to transgenerational transmission of obesity.


Subject(s)
Humans , Animals , Epigenesis, Genetic , Obesity/genetics , Histones , DNA Methylation , Genetic Predisposition to Disease , MicroRNAs/genetics , Diet
9.
Rev. méd. Chile ; 147(11): 1487-1490, nov. 2019. graf
Article in Spanish | LILACS | ID: biblio-1094178

ABSTRACT

The 2016 WHO Classification of Tumours of the Central Nervous System incorporates a new diagnostic entity: the mutant diffuse midline glioma H3K27, a tumor with a characteristic location and special molecular biology. We report the case of a 51-year-old male patient with progressive diplopia. The imaging study showed a mesencephalic tumor; the stereotacic biopsy disclosed an Anaplastic Astrocytoma Isocitrate dehydrogenase (IDH) wild type. The molecular study concludes H3K27 mutation. The patient was treated with radiotherapy with concurrent and adjuvant chemotherapy (temozolomide) with partial recovery of the diplopia.


Subject(s)
Humans , Male , Middle Aged , Brain Neoplasms/genetics , Histones/genetics , Glioma/genetics , Mutation/genetics , Brain Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Biomarkers, Tumor , Genetic Markers , Neuroimaging , Glioma/pathology , Glioma/diagnostic imaging
10.
Salud pública Méx ; 61(3): 318-328, may.-jun. 2019. tab, graf
Article in English | LILACS | ID: biblio-1094470

ABSTRACT

Abstract: Objective: To perform a systematic review of the main epigenetic aberrations involved in non-small cell lung carcinomas' (NSCLC) diagnosis, progression, and therapeutics. Materials and methods: We performed a systematic review of the scientific literature on lung cancer epigenetics, focusing on NSCLC. Results: Several advances in the molecular study of classical epigenetic mechanisms and massive studies of lung cancer epigenome have contributed relevant new evidence revealing that various molecular complexes are functionally influencing genetic-epigenetic and transcriptional mechanisms that promote lung tumorigenesis (initiation, promotion, and progression), and are also involved in NSCLC therapy-resistance mechanisms. Conclusion: Several epigenetic complexes and mechanisms must be analyzed and considered for the design of new and efficient therapies, which could be fundamental to develop an integrated knowledge to achieve a comprehensive lung cancer personalized medicine.


Resumen: Objetivo: Realizar una revisión sistemática y estructurada de las principales aberraciones epigenéticas involucradas en el diagnóstico, progresión y terapia del cáncer pulmonar de células no pequeñas (CPCNP). Material y métodos: Revisión sistemática de literatura científica sobre epigenética del cáncer pulmonar del grupo CPCNP. Resultados: El estudio de los diversos mecanismos epigenéticos y su impronta epigenética en el epigenoma del cáncer pulmonar han arrojado nuevas evidencias a nivel biológico, biomédico y médico-clínico del impacto que los mecanismos epigenético-transcripcionales promueven de manera activa y reversible sobre los procesos de tumorigénesis, progresión histopatológica y mecanismos de resistencia a la terapia oncológica pulmonar. Conclusión: Deben analizarse diferentes complejos y mecanismos epigenéticos para el estudio y diseño de esquemas nuevos y eficaces de terapia epigenética, los cuales podrían ser fundamentales para desarrollar un conocimiento integral en el desarrollo de la medicina personalizada en el cáncer pulmonar del grupo CPCNP.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Epigenesis, Genetic , Lung Neoplasms/genetics , Histones/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/therapy , Disease Progression , DNA Methylation/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy
11.
Article in English | WPRIM | ID: wpr-763335

ABSTRACT

OBJECTIVES: To investigate glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) gene expression and protein levels in peripheral blood mononuclear cells (PBMCs) of patients with severe or profound sudden sensorineural hearing loss (SSNHL) and to explore the roles of GRs and HDAC2 in glucocorticoid (GC) insensitivity. METHODS: Fifty-five severe or profound SSNHL patients were enrolled in the study. According to hearing improvement after GC treatment, patients were assigned into two groups: GC-sensitive and GC-resistant. A normal reference group included 20 healthy volunteers without hearing loss. Quantitative real-time polymerase chain reaction and Western blot analyses were used to detect the relative expression of GRα, GRβ, and HDAC2 in PBMCs at the mRNA and protein levels. RESULTS: The protein levels of GRs and HDAC2 in PBMCs of SSNHL patients were lower than the normal reference values before GC treatment. Compared with the GC-resistant group, both the mRNA and protein levels of GRα and HDAC2 were significantly increased in the GC-sensitive group after GC treatment. CONCLUSION: A lack of GRα and HDAC2 induction following steroid treatment in GC-resistant SSNHL patients may play a fundamental mechanistic role in GC insensitivity. Response of GRα and HDAC2 to steroid treatment may, thus, predict the prognosis of hearing improvement in SSNHL patients.


Subject(s)
Blotting, Western , Gene Expression , Healthy Volunteers , Hearing , Hearing Loss , Hearing Loss, Sensorineural , Histone Deacetylase 2 , Histone Deacetylases , Histones , Humans , Prognosis , Real-Time Polymerase Chain Reaction , Receptors, Glucocorticoid , Reference Values , RNA, Messenger
12.
Article in English | WPRIM | ID: wpr-763025

ABSTRACT

We attempted to examine anti-inflammatory and anti-oxidant effects of 4′-O-β-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin E₂ (PGE₂) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.


Subject(s)
Antioxidant Response Elements , Antioxidants , Cyclooxygenase 2 , Epigenomics , Free Radicals , Histones , Humans , In Vitro Techniques , Keratinocytes , Macrophages , NF-E2-Related Factor 2 , Nitric Oxide , Nitric Oxide Synthase Type II , Phosphorylation
13.
Article in English | WPRIM | ID: wpr-765052

ABSTRACT

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.


Subject(s)
Acetylation , Alzheimer Disease , Brain , Central Nervous System , Computational Biology , Diptera , Down-Regulation , Drosophila melanogaster , Drosophila , Heterochromatin , Histones , Humans , Locomotion , Methylation , Neurodegenerative Diseases , Neurofibrillary Tangles , Pathology , Phenotype , RNA, Messenger , tau Proteins , Tauopathies , Transcriptome
14.
Article in English | WPRIM | ID: wpr-764077

ABSTRACT

BACKGROUND AND OBJECTIVES: Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be a valuable source for cardiovascular tissue engineering and cell therapy. The aim of this study is to verify angiotensin II and transforming growth factor-beta 1 (TGF-β1) as potential cardiomyogenic differentiation inducers of AF-MSCs. METHODS AND RESULTS: AF-MSCs were obtained from amniocentesis samples from second-trimester pregnant women, isolated and characterized by the expression of cell surface markers (CD44, CD90, CD105 positive; CD34 negative) and pluripotency genes (OCT4, SOX2, NANOG, REX1). Cardiomyogenic differentiation was induced using different concentrations of angiotensin II and TGF-β1. Successful initiation of differentiation was confirmed by alterations in cell morphology, upregulation of cardiac genes-markers NKX2-5, TBX5, GATA4, MYH6, TNNT2, DES and main cardiac ion channels genes (sodium, calcium, potassium) as determined by RT-qPCR. Western blot and immunofluorescence analysis revealed the increased expression of Connexin43, the main component of gap junctions, and Nkx2.5, the early cardiac transcription factor. Induced AF-MSCs switched their phenotype towards more energetic and started utilizing oxidative phosphorylation more than glycolysis for energy production as assessed using Agilent Seahorse XF analyzer. The immune analysis of chromatin-modifying enzymes DNMT1, HDAC1/2 and Polycomb repressive complex 1 and 2 (PRC1/2) proteins BMI1, EZH2 and SUZ12 as well as of modified histones H3 and H4 indicated global chromatin remodeling during the induced differentiation. CONCLUSIONS: Angiotensin II and TGF-β1 are efficient cardiomyogenic inducers of human AF-MSCs; they initiate alterations at the gene and protein expression, metabolic and epigenetic levels in stem cells leading towards cardiomyocyte-like phenotype formation.


Subject(s)
Amniocentesis , Amniotic Fluid , Angiotensin II , Angiotensins , Blotting, Western , Calcium , Cell Differentiation , Cell- and Tissue-Based Therapy , Chromatin , Chromatin Assembly and Disassembly , Connexin 43 , Epigenomics , Female , Fluorescent Antibody Technique , Gap Junctions , Glycolysis , Histones , Humans , Ion Channels , Mesenchymal Stem Cells , Muscle Cells , Oxidative Phosphorylation , Phenotype , Polycomb Repressive Complex 1 , Pregnant Women , Smegmamorpha , Stem Cells , Tissue Engineering , Transcription Factors , Up-Regulation
15.
Neuroscience Bulletin ; (6): 216-224, 2019.
Article in English | WPRIM | ID: wpr-775435

ABSTRACT

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.


Subject(s)
Animals , Brain Stem Neoplasms , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cellular Senescence , Female , Glioma , Genetics , Metabolism , Pathology , Histones , Genetics , Humans , Mice, Inbred NOD , Mice, SCID , Neoplasm Transplantation , Neoplastic Stem Cells , Metabolism , Pathology , Neural Stem Cells , Metabolism , Pathology , Pons , Embryology , Metabolism , Pathology , Primary Cell Culture
16.
Article in Chinese | WPRIM | ID: wpr-771404

ABSTRACT

As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.


Subject(s)
Animals , Histones , Humans , Lysine , Neoplasms , Signal Transduction , Sirtuins , Metabolism
17.
Article in English | WPRIM | ID: wpr-772940

ABSTRACT

Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5' untranslated regions (5'UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.


Subject(s)
Acetylation , Base Sequence , Deoxyribonuclease I , Metabolism , Enhancer Elements, Genetic , Epigenesis, Genetic , Genes, Plant , Genomics , Methods , Histone Code , Genetics , Histones , Metabolism , Models, Genetic , Oryza , Genetics , Promoter Regions, Genetic , Genetics , Repetitive Sequences, Nucleic Acid , Genetics , Sequence Analysis, DNA , Transcription, Genetic
18.
Article in Chinese | WPRIM | ID: wpr-772690

ABSTRACT

Epigenetics is defined as a change in gene expression without the alteration of the genetic sequence. Such a change would be inherited by offspring. Histone acetylation is a type of epigenetics. Existing studies proposed that chronic periodontitis is related to epigenetic modification. In this review, we summarised the influence of chronic periodontitis on periodontal ligament stem cells by histone acetylation.


Subject(s)
Acetylation , Cell Differentiation , Cells, Cultured , Histones , Metabolism , Osteogenesis , Periodontal Ligament , Stem Cells , Physiology
19.
Article in English | WPRIM | ID: wpr-772264

ABSTRACT

There are large knowledge gaps regarding how to control stem cells growth and differentiation. The limitations of currently available technologies, such as growth factors and/or gene therapies has led to the search of alternatives. We explore here how a cell's epigenome influences determination of cell type, and potential applications in tissue engineering. A prevalent epigenetic modification is the acetylation of DNA core histone proteins. Acetylation levels heavily influence gene transcription. Histone deacetylase (HDAC) enzymes can remove these acetyl groups, leading to the formation of a condensed and more transcriptionally silenced chromatin. Histone deacetylase inhibitors (HDACis) can inhibit these enzymes, resulting in the increased acetylation of histones, thereby affecting gene expression. There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering, potentially providing novel tools to control stem cell fate. This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone, cardiac, neural tissues), including the history, current status and future perspectives of using HDACis for stem cell research and tissue engineering, with particular attention paid to how different HDAC isoforms may be integral to this field.


Subject(s)
Acetylation , Histone Deacetylase Inhibitors , Pharmacology , Histone Deacetylases , Metabolism , Histones , Metabolism , Humans , Tissue Engineering
20.
Article in English | WPRIM | ID: wpr-760610

ABSTRACT

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.


Subject(s)
Acetylation , Dietary Supplements , Epigenomics , Hep G2 Cells , Histone Acetyltransferases , Histones , Lipid Metabolism , Lipogenesis , Liver , Lysine , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , RNA, Messenger , Sterol Regulatory Element Binding Protein 1
SELECTION OF CITATIONS
SEARCH DETAIL