Epigenetics & Chromatin最新文献

{"title":"Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation.","authors":"Haley V Hobble, Christine E Schaner Tooley","doi":"10.1186/s13072-024-00530-0","DOIUrl":"10.1186/s13072-024-00530-0","url":null,"abstract":"<p><p>Protein and nucleic acid methylation are important biochemical modifications. In addition to their well-established roles in gene regulation, they also regulate cell signaling, metabolism, and translation. Despite this high biological relevance, little is known about the general regulation of methyltransferase function. Methyltransferases are divided into superfamilies based on structural similarities and further classified into smaller families based on sequence/domain/target similarity. While members within superfamilies differ in substrate specificity, their structurally similar active sites indicate a potential for shared modes of regulation. Growing evidence from one superfamily suggests a common regulatory mode may be through heterooligomerization with other family members. Here, we describe examples of methyltransferase regulation through intrafamily heterooligomerization and discuss how this can be exploited for therapeutic use.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"5"},"PeriodicalIF":3.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10908127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of SWI/SNF complex in breast cancer.","authors":"Kexuan Li, Baocai Wang, Haolin Hu","doi":"10.1186/s13072-024-00531-z","DOIUrl":"10.1186/s13072-024-00531-z","url":null,"abstract":"<p><p>In the past decade, numerous epigenetic mechanisms have been discovered to be associated with cancer. The mammalian SWI/SNF complex is an ATP-dependent chromatin remodeling complex whose mutations are associated with various malignancies including breast cancer. As the SWI/SNF complex has become one of the most commonly mutated complexes in cancer, targeting epigenetic mutations acquired during breast cancer progress is a potential means of improving clinical efficacy in treatment strategies. This article reviews the composition of the SWI/SNF complex, its main roles and research progress in breast cancer, and links these findings to the latest discoveries in cancer epigenomics to discuss the potential mechanisms and therapeutic potential of SWI/SNF in breast cancer.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"4"},"PeriodicalIF":3.9,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A low-input high resolution sequential chromatin immunoprecipitation method captures genome-wide dynamics of bivalent chromatin.","authors":"Janith A Seneviratne, William W H Ho, Eleanor Glancy, Melanie A Eckersley-Maslin","doi":"10.1186/s13072-024-00527-9","DOIUrl":"10.1186/s13072-024-00527-9","url":null,"abstract":"<p><strong>Background: </strong>Bivalent chromatin is an exemplar of epigenetic plasticity. This co-occurrence of active-associated H3K4me3 and inactive-associated H3K27me3 histone modifications on opposite tails of the same nucleosome occurs predominantly at promoters that are poised for future transcriptional upregulation or terminal silencing. We know little of the dynamics, resolution, and regulation of this chromatin state outside of embryonic stem cells where it was first described. This is partly due to the technical challenges distinguishing bone-fide bivalent chromatin, where both marks are on the same nucleosome, from allelic or sample heterogeneity where there is a mix of H3K4me3-only and H3K27me3-only mononucleosomes.</p><p><strong>Results: </strong>Here, we present a robust and sensitive method to accurately map bivalent chromatin genome-wide, along with controls, from as little as 2 million cells. We optimized and refined the sequential ChIP protocol which uses two sequential overnight immunoprecipitation reactions to robustly purify nucleosomes that are truly bivalent and contain both H3K4me3 and H3K27me3 modifications. Our method generates high quality genome-wide maps with strong peak enrichment and low background, which can be analyzed using standard bioinformatic packages. Using this method, we detect 8,789 bivalent regions in mouse embryonic stem cells corresponding to 3,918 predominantly CpG rich and developmentally regulated gene promoters. Furthermore, profiling Dppa2/4 knockout mouse embryonic stem cells, which lose both H3K4me3 and H3K27me3 at approximately 10% of bivalent promoters, demonstrated the ability of our method to capture bivalent chromatin dynamics.</p><p><strong>Conclusions: </strong>Our optimized sequential reChIP method enables high-resolution genome-wide assessment of bivalent chromatin together with all required controls in as little as 2 million cells. We share a detailed protocol and guidelines that will enable bivalent chromatin landscapes to be generated in a range of cellular contexts, greatly enhancing our understanding of bivalent chromatin and epigenetic plasticity beyond embryonic stem cells.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"3"},"PeriodicalIF":3.9,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells.","authors":"Alexander Calderon, Tamara Mestvirishvili, Francesco Boccalatte, Kelly V Ruggles, Gregory David","doi":"10.1186/s13072-024-00526-w","DOIUrl":"10.1186/s13072-024-00526-w","url":null,"abstract":"<p><strong>Background: </strong>Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignancy. In particular, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive. Previous studies have identified chromatin coordination as a key regulator of differentiation in embryonic stem cells.</p><p><strong>Results: </strong>Here, we utilized genetic inactivation of the chromatin-associated Sin3B protein to manipulate cell cycle control and found dysregulated chromatin accessibility and cell cycle progression in HSCs. Single cell transcriptional profiling of hematopoietic stem and progenitor cells (HSPCs) inactivated for Sin3B reveals aberrant progression through the G₁ phase of the cell cycle, which correlates with the engagement of specific signaling pathways, including aberrant expression of cell adhesion molecules and the interferon signaling program in LT-HSCs. In addition, we uncover the Sin3B-dependent accessibility of genomic elements controlling HSC differentiation, which points to cell cycle progression possibly dictating the priming of HSCs for differentiation.</p><p><strong>Conclusions: </strong>Our findings provide new insights into controlled cell cycle progression as a potential regulator of HSC lineage commitment through the modulation of chromatin features.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"2"},"PeriodicalIF":4.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of sex in immune response and epigenetic mechanisms.","authors":"Sombodhi Bhattacharya, Debasmita Sadhukhan, Radha Saraswathy","doi":"10.1186/s13072-024-00525-x","DOIUrl":"10.1186/s13072-024-00525-x","url":null,"abstract":"<p><p>The functioning of the human immune system is highly dependent on the sex of the individual, which comes by virtue of sex chromosomes and hormonal differences. Epigenetic mechanisms such as X chromosome inactivation, mosaicism, skewing, and dimorphism in X chromosome genes and Y chromosome regulatory genes create a sex-based variance in the immune response between males and females. This leads to differential susceptibility in immune-related disorders like infections, autoimmunity, and malignancies. Various naturally available immunomodulators are also available which target immune pathways containing X chromosome genes.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"1"},"PeriodicalIF":4.2,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects","authors":"Xue Li, Pei Pei, Jinying Shen, Juan Yu, Fang Wang, Lei Wang, Changyun Liu, Shan Wang","doi":"10.1186/s13072-023-00517-3","DOIUrl":"https://doi.org/10.1186/s13072-023-00517-3","url":null,"abstract":"Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined. Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis. Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"178 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation: the sweet side of epigenetics","authors":"Thomas Dupas, Benjamin Lauzier, Serge McGraw","doi":"10.1186/s13072-023-00523-5","DOIUrl":"https://doi.org/10.1186/s13072-023-00523-5","url":null,"abstract":"Histones display a wide variety of post-translational modifications, including acetylation, methylation, and phosphorylation. These epigenetic modifications can influence chromatin structure and function without altering the DNA sequence. Histones can also undergo post-translational O-GlcNAcylation, a rather understudied modification that plays critical roles in almost all biological processes and is added and removed by O-linked N-acetylglucosamine transferase and O-GlcNAcase, respectively. This review provides a current overview of our knowledge of how O-GlcNAcylation impacts the histone code both directly and by regulating other chromatin modifying enzymes. This highlights the pivotal emerging role of O-GlcNAcylation as an essential epigenetic marker.","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"6 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the list of sequence-agnostic enzymes for chromatin conformation capture assays with S1 nuclease","authors":"Gridina Maria, Popov Andrey, Shadskiy Artem, Torgunakov Nikita, Kechin Andrey, Khrapov Evgeny, Ryzhkova Oxana, Filipenko Maxim, Fishman Veniamin","doi":"10.1186/s13072-023-00524-4","DOIUrl":"https://doi.org/10.1186/s13072-023-00524-4","url":null,"abstract":"This study presents a novel approach for mapping global chromatin interactions using S1 nuclease, a sequence-agnostic enzyme. We develop and outline a protocol that leverages S1 nuclease's ability to effectively introduce breaks into both open and closed chromatin regions, allowing for comprehensive profiling of chromatin properties. Our S1 Hi–C method enables the preparation of high-quality Hi–C libraries, marking a significant advancement over previously established DNase I Hi–C protocols. Moreover, S1 nuclease's capability to fragment chromatin to mono-nucleosomes suggests the potential for mapping the three-dimensional organization of the genome at high resolution. This methodology holds promise for an improved understanding of chromatin state-dependent activities and may facilitate the development of new genomic methods.","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"26 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138565691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functions of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) in biological process and disease.","authors":"Hanshen Luo, Xingliang Wu, Xue-Hai Zhu, Xin Yi, Dunfeng Du, Ding-Sheng Jiang","doi":"10.1186/s13072-023-00519-1","DOIUrl":"10.1186/s13072-023-00519-1","url":null,"abstract":"<p><p>Histone methyltransferase SETDB1 (SET domain bifurcated histone lysine methyltransferase 1, also known as ESET or KMT1E) is known to be involved in the deposition of the di- and tri-methyl marks on H3K9 (H3K9me2 and H3K9me3), which are associated with transcription repression. SETDB1 exerts an essential role in the silencing of endogenous retroviruses (ERVs) in embryonic stem cells (mESCs) by tri-methylating H3K9 (H3K9me3) and interacting with DNA methyltransferases (DNMTs). Additionally, SETDB1 is engaged in regulating multiple biological processes and diseases, such as ageing, tumors, and inflammatory bowel disease (IBD), by methylating both histones and non-histone proteins. In this review, we provide an overview of the complex biology of SETDB1, review the upstream regulatory mechanisms of SETDB1 and its partners, discuss the functions and molecular mechanisms of SETDB1 in cell fate determination and stem cell, as well as in tumors and other diseases. Finally, we discuss the current challenges and prospects of targeting SETDB1 for the treatment of different diseases, and we also suggest some future research directions in the field of SETDB1 research.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"47"},"PeriodicalIF":3.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10702034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138499900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin balances cell redox and energy homeostasis.","authors":"Tamaki Suganuma, Jerry L Workman","doi":"10.1186/s13072-023-00520-8","DOIUrl":"10.1186/s13072-023-00520-8","url":null,"abstract":"<p><p>Chromatin plays a central role in the conversion of energy in cells: alteration of chromatin structure to make DNA accessible consumes energy, and compaction of chromatin preserves energy. Alteration of chromatin structure uses energy sources derived from carbon metabolism such as ATP and acetyl-CoA; conversely, chromatin compaction and epigenetic modification feedback to metabolism and energy homeostasis by controlling gene expression and storing metabolites. Coordination of these dual chromatin events must be flexibly modulated in response to environmental changes such as during development and exposure to stress. Aging also alters chromatin structure and the coordination of metabolism, chromatin dynamics, and other cell processes. Noncoding RNAs and other RNA species that associate directly with chromatin or with chromatin modifiers contribute to spatiotemporal control of transcription and energy conversion. The time required for generating the large amounts of RNAs and chromatin modifiers observed in super-enhancers may be critical for regulation of transcription and may be impacted by aging. Here, taking into account these factors, we review alterations of chromatin that are fundamental to cell responses to metabolic changes due to stress and aging to maintain redox and energy homeostasis. We discuss the relationship between spatiotemporal control of energy and chromatin function, as this emerging concept must be considered to understand how cell homeostasis is maintained.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"16 1","pages":"46"},"PeriodicalIF":3.9,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}