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Myopia has become a serious public health problem, but its pathogenesis is still unclear, and effective interventions are relatively scarce.It is recognized that myopia is influenced by both genetic and environmental factors, in which epigenetics may play a key role.Epigenetics refers to the changes in gene expression and function that do not involve DNA sequence variation.Mainly including DNA methylation, non-coding RNA (microRNA, long non-coding RNA and circular RNA, etc.), histone modification and mRNA modification, epigenetic modifications interact to form a complex regulatory network in the pathophysiological process of myopia.By controlling the process of scleral matrix remodeling, eye cell proliferation and retinal development, the morphological characteristics of the eye are jointly regulated, ultimately affecting the onset and development of myopia.Epigenetics has provided new targets of myopia intervention and has become a hotspot in the field.In this paper, we reviewed the current findings of myopia epigenetics to provide a reference for related research.
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Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.
Subject(s)
Female , Humans , Endometriosis/genetics , Epigenesis, Genetic , DNA Methylation , Protein Processing, Post-TranslationalABSTRACT
Chinese hamster ovary (CHO) cells play an irreplaceable role in biopharmaceuticals because the cells can be adapted to grow in suspension cultures and are capable of producing high quality biologics exhibiting human-like post-translational modifications. However, gene expression regulation such as transgene silencing and epigenetic modifications may reduce the recombinant protein production due to the decrease of expression stability of CHO cells. This paper summarized the role of epigenetic modifications in CHO cells, including DNA methylation, histone modification and miRNA, as well as their effects on gene expression regulation.
Subject(s)
Cricetinae , Animals , Humans , Cricetulus , CHO Cells , Epigenesis, Genetic/genetics , DNA Methylation , Gene Expression Regulation , Recombinant Proteins/geneticsABSTRACT
As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.
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Objective: Recently, epigenetic mechanisms related to histone modifications including histone deacetylation (HDAC) have been emphasized in psychiatric diseases. Few studies have investigated the relationship of HDAC gene variations to psychiatric diseases, but these gene variations have never been studied in obsessive-compulsive disorder (OCD). The present case-control study aimed to compare symptomatology with HDAC gene variations in patients with OCD. Methods: Illumina next-generation sequencing of six HDAC genes (HDAC2,3,4,9,10,11) was performed on DNA samples isolated from 200 Turkish subjects recruited from routine clinical practice. Twenty-seven single nucleotide polymorphism (SNPs) in six HDAC genes were scanned with the LightSNiP method. Results: New variants, all previously unreported in the literature, were identified in the HDAC4, HDAC10, and HDAC11 genes. When control and OCD patient groups were compared, a statistically significant difference was found in HDAC2 rs13212283, HDAC4 rs1063639, and HDAC10 rs1555048 in terms of genotype distribution (p < 0.05). In addition, in the OCD group, a statistically significant relationship was found between some obsessions/compulsions and HDAC2, HDAC3, and HDAC4 polymorphisms (p < 0.05). Conclusions: Our study shows that the HDAC2, HDAC3, HDAC4, and HDAC10 genes may play a role in the pathogenesis of OCD.
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Pancreatic ductal adenocarcinoma is one of the most common malignant tumors. Its early diagnosis and treatment are very difficult, and the mortality and recurrence rate are high. Chronic pancreatitis is an important risk factor for pancreatic cancer and has great potential to develop into pancreatic cancer. Therefore, it is necessary to study the mechanism of pancreatitis-cancer transformation for early diagnosis and treatment of pancreatic cancer. In recent years, more and more studies have shown that epigenetic modification plays an important role in pancreatitis-cancer transformation, and can provide an effective target for the diagnosis and treatment of pancreatic cancer. This article summarizes the role and mechanism of epigenetics in pancreatitis-cancer transformation based on the current research progress.
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In neuronal system, epigenetic modifications are essential for neuronal development, the fate determination of neural stem cells and neuronal function. The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease. Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington's disease. In the brain of Alzheimer's disease patients, the levels of H3K27ac and H3K9ac histone modifications increased. In addition, the alteration of RNA methylation in animal models of Alzheimer's disease and Parkinson's disease showed discrepancy trends. Therefore, epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases. Here, we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.
Subject(s)
Animals , Humans , DNA Methylation , Epigenesis, Genetic , Neurodegenerative Diseases/genetics , Parkinson Disease/genetics , Protein Processing, Post-TranslationalABSTRACT
Epigenetics concerns gene regulatory mechanisms beyond DNA sequence，such as DNA methylation，histone modification，chromatin remodeling，and non-coding RNA. Epigenetic mechanisms play a key role in development，cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information，and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis，increased glucose uptake，abnormally active glutamine metabolism，and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer，and help tumor cells adapt to hypoxia microenvironment for their survival，proliferation，invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand，metabolites in tumor cells may act as cofactors，modification donors or antagonists of epigenetic enzymes，thus modulating the epigenetic landscape. On the other hand，epigenetic modifications can directly regulate the expression of metabolic enzymes，transporters，signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism，to explore their potential future applications in the treatment of tumors.
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Humans , Carcinogenesis , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation , Neoplasms/genetics , Tumor MicroenvironmentABSTRACT
Histone modifications play a critical role in coordinating accurate gene expression. Aside from geneticmutations which cause altered DNA sequence, it has become increasingly clear that aberrant post-translationalmodifications of histone tails are also associated with leukemogenesis. The functional roles of specific histonemarks has informed the basis of our understanding for underlying mechanisms of leukemia, while globalanalyses of interacting histone modifications has begun to distinguish subtypes of leukemia with prognosticand therapeutic implications. In this current era of personalized and precision medicine, it will be necessary tonot only identify the specific genetic mutations present in a patient’s leukemia but to also appreciate thedynamic chromatin states which are driven by histone modifications that can aid our diagnostic and therapeuticstrategies for improved management of leukemia.
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Under nutritional stress, cells undergo metabolic rewiring that results in changes of various cellular processesthat include gene transcription. This transcriptional regulation requires dynamic chromatin remodeling thatinvolves histone post-translational modifications. There are several histone marks that may act as switchesupon starvation for stress-response pathways.
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Epigenetics refers to the heritable changes of gene expression without altering DNA sequence.Epigentic mechanism involves DNA methylation,microRNA,histone modification and so on.Tetralogy of Fallot (TOF) is a common congenital heart disease characterized by ventricular septal defect,pulmonary stenosis,aortic straddling and right ventricular hypertrophy.Many experimental investigations indicate that epigentics plays an important role in the development of the heart.It will be an important research field in the future showing important clinical significance to study the etiology of tetralogy of Fallot.
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@#In recent decades, although great progress has been made on the diagnosis and treatment of oral squamous cell carcinoma (OSCC), its 5-year survival rate has not been significantly improved. The basic reason is the unclear pathogenesis, lack of effective molecular markers for assessing invasion, metastasis, and recurrence as well as therapeutic targets. The present view is that genetic and epigenetic abnormalities are related to the occurrence and development of OSCC. Epigenetic inheritance is a biological behavior that can be regulated and reversed, and it plays an important role in the occurrence and development of malignant tumors. First, this review will describe the role of epigenetic modifications in the development of OSCC in combination with our research and the latest research progress of epigenetics, including DNA methylation, RNA methylation, short noncoding RNAs (miRNAs, etc.), long noncoding RNAs, circular RNAs, histone modifications (acetylation and methylation), chromatin remodeling and genomic imprinting. Then, we will analyze the value of epigenetic studies in the prevention, diagnosis, and targeted therapy of OSCC.
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BACKGROUND: Inflammatory bowel disease is a chronic inflammatory disease associated with intestinal immune, and autophagy is a cell approach to promote immune regulation. Abnormal expression of autophagy-related genes is closely related to intestinal inflammation and immune response. However, the mechanism by which epigenetic modification regulates autophagy in inflammatory bowel disease has not been fully clarified. OBJECTIVE: To introduce the role of epigenetic modification in autophagy, and to promote a further understanding of inflammatory bowel disease. METHODS: A computer-based online research of PubMed database was performed with the key words of “inflammatory bowel disease, autophagy, autophagy-related genes, epigenetic modification, DNA methylation, histone modification, chromatin remodeling, miRNA.” The search time was from January 1998 to April 2019. Finally, 61 eligible articles were included in result analysis. RESULTS AND CONCLUSION: Epigenetic modifications such as DNA methylation, histone modification, chromatin remodeling, non-coding RNA can regulate intestinal inflammation, immune and autophagy through susceptibility genes AGL and IRGM, thereby mediating the occurrence and development of inflammatory bowel disease.
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Heart failure(HF)is the terminal stage of cardiovascular diseases and has long been one of the most deadly condition due to its high morbidity and mortality.Since the currently available treatment options cannot meet the clinical needs,new therapeutic strategies for HF should be actively explored.Epigenetics does not involve the changes of genetic sequences but focuses on the stable inheritance of genes in different individuals.It is affected by the interaction between genes and environments,which may result in DNA methylation,histone modification,and other changes.This article summarizes the recent research advances in epigenetics in HF.
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Acupuncture has been widely used for treating diseases since the ancient days in China, but the mechanism by which acupuncture exerts such powerful roles is unclear. Epigenetics, including DNA methylation, histone modification, and post-transcriptional regulation of miRNAs, is the study of heritable changes in gene expression that do not include DNA sequence alterations. Epigenetics has become a new strategy for the basic and clinical research of acupuncture in the last decade. Some investigators have been trying to illustrate the mechanism of acupuncture from an epigenetics perspective, which has shed new lights on the mechanisms and applications of acupuncture. Moreover, the introduction of epigenetics into the regulatory mechanism in acupuncture treatment has provided more objective and scientific support for acupuncture theories and brought new opportunities for the improvement of acupuncture studies. In this paper, we reviewed the literatures that has demonstrated that acupuncture could directly or indirectly affect epigenetics, in order to highlight the progress of acupuncture studies correlated to epigenetic regulations. We do have to disclose that the current evidence in this review is not enough to cover all the complex interactions between multiple epigenetic modifications and their regulations. However, the up-to-date results can help us to better understand acupuncture's clinical applications and laboratory research.
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Epigenetics refers to the heritable changes of gene expression without altering DNA sequence.Epigentic mechanism involves DNA methylation, microRNA, histone modification and so on.Tetralogy of Fallot(TOF)is a common congenital heart disease characterized by ventricular septal defect, pulmonary stenosis, aortic straddling and right ventricular hypertrophy.Many experimental investigations indicate that epigentics plays an important role in the development of the heart.It will be an important research field in the future showing important clinical significance to study the etiology of tetralogy of Fallot.
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Pneumoconiosis is the most common and severe occupational disease, has become a major public health problem in the world. Its causes are well known, but the pathogenesis of it is not completely clear and effective therapies are not currently available. Epigenetic modifications have been considered an initial event in the development of pneumoconiosis. Epigenetic regulatory mechanisms in pneumoconiosis include DNA methylation, non-coding RNA (ncRNA) , and histone modification. In recent years, many researchers have studied the effect of dust-induced pulmonary fibrosis-related gene expression at the epigenetic level on macrophage activation, lung fibroblast proliferation, activation, transdifferentiation, and epithelial or endothelial-mesenchymal transition (EMT/EndMT) to further elucidate the pathogenesis of pneumoconiosis. In this review, we discusses the epigenetic modifications in pneumoconiosis, with an aim to provide new insights into the early diagnosis, condition assessment and targeted therapy of this occupational disease.
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OBJECTIVE@#To optimize DNA library construction in non-crosslinked chromatin immunoprecipitation coupled with next-generation sequencing (Native ChIP-seq) to obtain high-quality Native ChIP-seq data.@*METHODS@#Human nasopharyngeal carcinoma HONE1 cell lysate was digested with MNase for release of the nucleosomes, and the histone-DNA complexes were immunoprecipitated with specific antibodies. The protein component in the precipitate was digested with proteinase K followed by DNA purification; the DNA library was constructed for sequence analysis.@*RESULTS@#Compared with the conventional DNA library construction, Tn5 transposase method allowed direct enrichment of the target DNA after Tn5 fragmentation, which was simple, time-saving and more efficient. The IGV visualized map showed that the information obtained by the two library construction methods was consistent. The sequencing data obtained by the two methods revealed more signal enrichment with Tn5 transposase library construction than with the conventional approach. H3K4me3 ChIP results showed a good reproducibility after Tn5 transposase library construction with a signal-to-noise ratio above 50%.@*CONCLUSIONS@#Tn5 transposase method improves the efficiency of DNA library construction and the results of subsequent sequence analysis, and is especially suitable for detecting histone modification in the DNA to provide a better technical option for epigenetic studies.
Subject(s)
Humans , Chromatin Immunoprecipitation , DNA , Gene Library , High-Throughput Nucleotide Sequencing , Reproducibility of Results , Sequence Analysis, DNAABSTRACT
Drosophila neural development undergoes extensive chromatin remodeling and precise epigenetic regulation. However, the roles of chromatin remodeling in establishment and maintenance of cell identity during cell fate transition remain enigmatic. Here, we compared the changes in gene expression, as well as the dynamics of nucleosome positioning and key histone modifications between the four major neural cell types during Drosophila neural development. We find that the neural progenitors can be separated from the terminally differentiated cells based on their gene expression profiles, whereas nucleosome distribution in the flanking regions of transcription start sites fails to identify the relationships between the progenitors and the differentiated cells. H3K27me3 signal in promoters and enhancers can not only distinguish the progenitors from the differentiated cells but also identify the differentiation path of the neural stem cells (NSCs) to the intermediate progenitor cells to the glial cells. In contrast, H3K9ac signal fails to identify the differentiation path, although it activates distinct sets of genes with neuron-specific and glia-related functions during the differentiation of the NSCs into neurons and glia, respectively. Together, our study provides novel insights into the crucial roles of chromatin remodeling in determining cell type during Drosophila neural development.
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Epigenetic modifications represent an important mechanism underlying regulation of gene expression that enables human body to adapt to the changing environment. Research methods of epigenetic modifications are a frontier area for the study of molecular mechanisms underlying the pathogenesis of autoimmune diseases. Rheumatoid arthritis ( RA) has been one of the difficulties in both clinical and basic-research fields of autoimmune diseases. Hie etiology of RA remains elusive, and its pathogenesis involves complex immune and inflammatory pathways. Clinically ideal therapeutic approaches are still lacking for treatment of RA. Recent studies have shown that Chinese herbal medicine and bioactive components there of potentially target ep-igenetic modifications in the treatment of RA. In order to provide new research ideas for therapeutic interventions and mechanistic studies of RA, we here reviewed and summarized literature on the epigenetic mechanism underlying the generation and development of RA and therapeutic effects of Chinese herbal medicine in RA that involve targeting epigenetic modifications.