Epigenetics & Chromatin最新文献

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Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells. 长期暴露于柴油废气颗粒会诱导人类腺癌肺泡基底上皮细胞的 DNA 甲基化和转录组发生一致的变化。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-08-05 DOI: 10.1186/s13072-024-00549-3
Alexandra Lukyanchuk, Naomi Muraki, Tomoko Kawai, Takehiro Sato, Kenichiro Hata, Tsuyoshi Ito, Atsushi Tajima
{"title":"Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells.","authors":"Alexandra Lukyanchuk, Naomi Muraki, Tomoko Kawai, Takehiro Sato, Kenichiro Hata, Tsuyoshi Ito, Atsushi Tajima","doi":"10.1186/s13072-024-00549-3","DOIUrl":"10.1186/s13072-024-00549-3","url":null,"abstract":"<p><strong>Background: </strong>Diesel exhaust particles (DEP), which contain hazardous compounds, are emitted during the combustion of diesel. As approximately one-third of the vehicles worldwide use diesel, there are growing concerns about the risks posed by DEP to human health. Long-term exposure to DEP is associated with airway hyperresponsiveness, pulmonary fibrosis, and inflammation; however, the molecular mechanisms behind the effects of DEP on the respiratory tract are poorly understood. Such mechanisms can be addressed by examining transcriptional and DNA methylation changes. Although several studies have focused on the effects of short-term DEP exposure on gene expression, research on the transcriptional effects and genome-wide DNA methylation changes caused by long-term DEP exposure is lacking. Hence, in this study, we investigated transcriptional and DNA methylation changes in human adenocarcinoma alveolar basal epithelial A549 cells caused by prolonged exposure to DEP and determined whether these changes are concordant.</p><p><strong>Results: </strong>DNA methylation analysis using the Illumina Infinium MethylationEPIC BeadChips showed that the methylation levels of DEP-affected CpG sites in A549 cells changed in a dose-dependent manner; the extent of change increased with increasing dose reaching the statistical significance only in samples exposed to 30 µg/ml DEP. Four-week exposure to 30 µg/ml of DEP significantly induced DNA hypomethylation at 24,464 CpG sites, which were significantly enriched for DNase hypersensitive sites, genomic regions marked by H3K4me1 and H3K27ac, and several transcription factor binding sites. In contrast, 9,436 CpG sites with increased DNA methylation levels were significantly overrepresented in genomic regions marked by H3K27me3 as well as H3K4me1 and H3K27ac. In parallel, gene expression profiling by RNA sequencing demonstrated that long-term exposure to DEP altered the expression levels of 2,410 genes, enriching 16 gene sets including Xenobiotic metabolism, Inflammatory response, and Senescence. In silico analysis revealed that the expression levels of 854 genes correlated with the methylation levels of the DEP-affected cis-CpG sites.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first report of genome-wide transcriptional and DNA methylation changes and their associations in A549 cells following long-term exposure to DEP.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"24"},"PeriodicalIF":4.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894722","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}
引用次数: 0
The role of ribosomal DNA methylation in embryonic development, aging and diseases. 核糖体 DNA 甲基化在胚胎发育、衰老和疾病中的作用。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-07-31 DOI: 10.1186/s13072-024-00548-4
Fei Yang, Xutong Guo, Yiming Bao, Rujiao Li
{"title":"The role of ribosomal DNA methylation in embryonic development, aging and diseases.","authors":"Fei Yang, Xutong Guo, Yiming Bao, Rujiao Li","doi":"10.1186/s13072-024-00548-4","DOIUrl":"10.1186/s13072-024-00548-4","url":null,"abstract":"<p><p>The ribosomal DNA (rDNA) constitutes a remarkably conserved DNA sequence within species, located in the area of the nucleolus, and responsible for coding three major types of rRNAs (18S, 5.8S and 28S). While historical investigations into rDNA focused on its structure and coding capabilities, recent research has turned to explore its functional roles in various biological processes. In this review, we summarize the main findings of rDNA methylation with embryonic development, aging and diseases in multiple species, including epigenetic alterations, related biological processes and potential applications of rDNA methylation. We present an overview of current related research and identify gaps in this field.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"23"},"PeriodicalIF":4.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861402","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}
引用次数: 0
CUT&Tag applied to zebrafish adult tail fins reveals a return of embryonic H3K4me3 patterns during regeneration. 将 CUT&Tag 应用于斑马鱼成体尾鳍,可发现再生过程中胚胎期 H3K4me3 模式的回归。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-07-20 DOI: 10.1186/s13072-024-00547-5
Phu Duong, Anjelica Rodriguez-Parks, Junsu Kang, Patrick J Murphy
{"title":"CUT&Tag applied to zebrafish adult tail fins reveals a return of embryonic H3K4me3 patterns during regeneration.","authors":"Phu Duong, Anjelica Rodriguez-Parks, Junsu Kang, Patrick J Murphy","doi":"10.1186/s13072-024-00547-5","DOIUrl":"10.1186/s13072-024-00547-5","url":null,"abstract":"<p><p>Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains only partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of changes in chromatin modifications during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-h old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"22"},"PeriodicalIF":4.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735481","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}
引用次数: 0
CREdb: A comprehensive database of Cis-Regulatory Elements and their activity in human cells and tissues. CREdb:顺式调控元件及其在人体细胞和组织中的活性的综合数据库。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-07-16 DOI: 10.1186/s13072-024-00545-7
Chris Hartl, Jiali Zhuang, Aaron Tyler, Bing Zhou, Emily Wong, David Merberg, Brad Farrell, Chris DeBoever, Julie Bryant, Dorothée Diogo
{"title":"CREdb: A comprehensive database of Cis-Regulatory Elements and their activity in human cells and tissues.","authors":"Chris Hartl, Jiali Zhuang, Aaron Tyler, Bing Zhou, Emily Wong, David Merberg, Brad Farrell, Chris DeBoever, Julie Bryant, Dorothée Diogo","doi":"10.1186/s13072-024-00545-7","DOIUrl":"10.1186/s13072-024-00545-7","url":null,"abstract":"<p><strong>Background: </strong>Cis-regulatory elements (CREs) play a pivotal role in gene expression regulation, allowing cells to serve diverse functions and respond to external stimuli. Understanding CREs is essential for personalized medicine and disease research, as an increasing number of genetic variants associated with phenotypes and diseases overlap with CREs. However, existing databases often focus on subsets of regulatory elements and present each identified instance of element individually, confounding the effort to obtain a comprehensive view. To address this gap, we have created CREdb, a comprehensive database with over 10 million human regulatory elements across 1,058 cell types and 315 tissues harmonized from different data sources. We curated and aligned the cell types and tissues to standard ontologies for efficient data query.</p><p><strong>Results: </strong>Data from 11 sources were curated and mapped to standard ontological terms. 11,223,434 combined elements are present in the final database, and these were merged into 5,666,240 consensus elements representing the combined ranges of the individual elements informed by their overlap. Each consensus element contains curated metadata including the number of elements supporting it and a hash linking to the source databases. The inferred activity of each consensus element in various cell-type and tissue context is also provided. Examples presented here show the potential utility of CREdb in annotating non-coding genetic variants and informing chromatin accessibility profiling analysis.</p><p><strong>Conclusions: </strong>We developed CREdb, a comprehensive database of CREs, to simplify the analysis of CREs by providing a unified framework for researchers. CREdb compiles consensus ranges for each element by integrating the information from all instances identified across various source databases. This unified database facilitates the functional annotation of non-coding genetic variants and complements chromatin accessibility profiling analysis. CREdb will serve as an important resource in expanding our knowledge of the epigenome and its role in human diseases.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"21"},"PeriodicalIF":4.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141628156","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}
引用次数: 0
Imprinted DNA methylation of the H19 ICR is established and maintained in vivo in the absence of Kaiso 在没有 Kaiso 的情况下,体内 H19 ICR 的印迹 DNA 甲基化得以建立和维持
IF 3.9 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-06-05 DOI: 10.1186/s13072-024-00544-8
Hitomi Matsuzaki, Minami Kimura, Mizuki Morihashi, Keiji Tanimoto
{"title":"Imprinted DNA methylation of the H19 ICR is established and maintained in vivo in the absence of Kaiso","authors":"Hitomi Matsuzaki, Minami Kimura, Mizuki Morihashi, Keiji Tanimoto","doi":"10.1186/s13072-024-00544-8","DOIUrl":"https://doi.org/10.1186/s13072-024-00544-8","url":null,"abstract":"Paternal allele-specific DNA methylation of the imprinting control region (H19 ICR) controls genomic imprinting at the Igf2/H19 locus. We previously demonstrated that the mouse H19 ICR transgene acquires imprinted DNA methylation in preimplantation mouse embryos. This activity is also present in the endogenous H19 ICR and protects it from genome-wide reprogramming after fertilization. We also identified a 118-bp sequence within the H19 ICR that is responsible for post-fertilization imprinted methylation. Two mutations, one in the five RCTG motifs and the other a 36-bp deletion both in the 118-bp segment, caused complete and partial loss, respectively, of methylation following paternal transmission in each transgenic mouse. Interestingly, these mutations overlap with the binding site for the transcription factor Kaiso, which is reportedly involved in maintaining paternal methylation at the human H19 ICR (IC1) in cultured cells. In this study, we investigated if Kaiso regulates imprinted DNA methylation of the H19 ICR in vivo. Neither Kaiso deletion nor mutation of Kaiso binding sites in the 118-bp region affected DNA methylation of the mouse H19 ICR transgene. The endogenous mouse H19 ICR was methylated in a wild-type manner in Kaiso-null mutant mice. Additionally, the human IC1 transgene acquired imprinted DNA methylation after fertilization in the absence of Kaiso. Our results indicate that Kaiso is not essential for either post-fertilization imprinted DNA methylation of the transgenic H19 ICR in mouse or for methylation imprinting of the endogenous mouse H19 ICR.","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259000","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}
引用次数: 0
Native and tagged CENP-A histones are functionally inequivalent. 原生组蛋白和标记的 CENP-A 组蛋白在功能上是不等同的。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-06-02 DOI: 10.1186/s13072-024-00543-9
Minh Bui, Songjoon Baek, Reda S Bentahar, Daniël P Melters, Yamini Dalal
{"title":"Native and tagged CENP-A histones are functionally inequivalent.","authors":"Minh Bui, Songjoon Baek, Reda S Bentahar, Daniël P Melters, Yamini Dalal","doi":"10.1186/s13072-024-00543-9","DOIUrl":"10.1186/s13072-024-00543-9","url":null,"abstract":"<p><strong>Background: </strong>Over the past several decades, the use of biochemical and fluorescent tags has elucidated mechanistic and cytological processes that would otherwise be impossible. The challenging nature of certain nuclear proteins includes low abundancy, poor antibody recognition, and transient dynamics. One approach to get around those issues is the addition of a peptide or larger protein tag to the target protein to improve enrichment, purification, and visualization. However, many of these studies were done under the assumption that tagged proteins can fully recapitulate native protein function.</p><p><strong>Results: </strong>We report that when C-terminally TAP-tagged CENP-A histone variant is introduced, it undergoes altered kinetochore protein binding, differs in post-translational modifications (PTMs), utilizes histone chaperones that differ from that of native CENP-A, and can partially displace native CENP-A in human cells. Additionally, these tagged CENP-A-containing nucleosomes have reduced centromeric incorporation at early G1 phase and poorly associates with linker histone H1.5 compared to native CENP-A nucleosomes.</p><p><strong>Conclusions: </strong>These data suggest expressing tagged versions of histone variant CENP-A may result in unexpected utilization of non-native pathways, thereby altering the biological function of the histone variant.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"19"},"PeriodicalIF":4.2,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201093","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}
引用次数: 0
From compartments to loops: understanding the unique chromatin organization in neuronal cells. 从区室到环路:了解神经元细胞中独特的染色质组织。
IF 4.2 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-05-23 DOI: 10.1186/s13072-024-00538-6
Diana Zagirova, Anna Kononkova, Nikita Vaulin, Ekaterina Khrameeva
{"title":"From compartments to loops: understanding the unique chromatin organization in neuronal cells.","authors":"Diana Zagirova, Anna Kononkova, Nikita Vaulin, Ekaterina Khrameeva","doi":"10.1186/s13072-024-00538-6","DOIUrl":"10.1186/s13072-024-00538-6","url":null,"abstract":"<p><p>The three-dimensional organization of the genome plays a central role in the regulation of cellular functions, particularly in the human brain. This review explores the intricacies of chromatin organization, highlighting the distinct structural patterns observed between neuronal and non-neuronal brain cells. We integrate findings from recent studies to elucidate the characteristics of various levels of chromatin organization, from differential compartmentalization and topologically associating domains (TADs) to chromatin loop formation. By defining the unique chromatin landscapes of neuronal and non-neuronal brain cells, these distinct structures contribute to the regulation of gene expression specific to each cell type. In particular, we discuss potential functional implications of unique neuronal chromatin organization characteristics, such as weaker compartmentalization, neuron-specific TAD boundaries enriched with active histone marks, and an increased number of chromatin loops. Additionally, we explore the role of Polycomb group (PcG) proteins in shaping cell-type-specific chromatin patterns. This review further emphasizes the impact of variations in chromatin architecture between neuronal and non-neuronal cells on brain development and the onset of neurological disorders. It highlights the need for further research to elucidate the details of chromatin organization in the human brain in order to unravel the complexities of brain function and the genetic mechanisms underlying neurological disorders. This research will help bridge a significant gap in our comprehension of the interplay between chromatin structure and cell functions.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"18"},"PeriodicalIF":4.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11112951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089231","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}
引用次数: 0
Chromatin profiling and state predictions reveal insights into epigenetic regulation during early porcine development. 染色质分析和状态预测揭示了猪早期发育过程中的表观遗传调控。
IF 3.9 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-05-21 DOI: 10.1186/s13072-024-00542-w
Sarah M Innis, Ryan A Cabot
{"title":"Chromatin profiling and state predictions reveal insights into epigenetic regulation during early porcine development.","authors":"Sarah M Innis, Ryan A Cabot","doi":"10.1186/s13072-024-00542-w","DOIUrl":"10.1186/s13072-024-00542-w","url":null,"abstract":"<p><strong>Background: </strong>Given their physiological similarities to humans, pigs are increasingly used as model organisms in human-oriented biomedical studies. Additionally, their value to animal agriculture across the globe has led to the development of numerous studies to investigate how to improve livestock welfare and production efficiency. As such, pigs are uniquely poised as compelling models that can yield findings with potential implications in both human and animal contexts. Despite this, many gaps remain in our knowledge about the foundational mechanisms that govern gene expression in swine across different developmental stages, particularly in early development. To address some of these gaps, we profiled the histone marks H3K4me3, H3K27ac, and H3K27me3 and the SWI/SNF central ATPase BRG1 in two porcine cell lines representing discrete early developmental time points and used the resulting information to construct predicted chromatin state maps for these cells. We combined this approach with analysis of publicly available RNA-seq data to examine the relationship between epigenetic status and gene expression in these cell types.</p><p><strong>Results: </strong>In porcine fetal fibroblast (PFF) and trophectoderm cells (PTr2), we saw expected patterns of enrichment for each of the profiled epigenetic features relative to specific genomic regions. H3K4me3 was primarily enriched at and around global gene promoters, H3K27ac was enriched in promoter and intergenic regions, H3K27me3 had broad stretches of enrichment across the genome and narrower enrichment patterns in and around the promoter regions of some genes, and BRG1 primarily had detectable enrichment at and around promoter regions and in intergenic stretches, with many instances of H3K27ac co-enrichment. We used this information to perform genome-wide chromatin state predictions for 10 different states using ChromHMM. Using the predicted chromatin state maps, we identified a subset of genomic regions marked by broad H3K4me3 enrichment, and annotation of these regions revealed that they were highly associated with essential developmental processes and consisted largely of expressed genes. We then compared the identities of the genes marked by these regions to genes identified as cell-type-specific using transcriptome data and saw that a subset of broad H3K4me3-marked genes was also specifically expressed in either PFF or PTr2 cells.</p><p><strong>Conclusions: </strong>These findings enhance our understanding of the epigenetic landscape present in early swine development and provide insight into how variabilities in chromatin state are linked to cell identity. Furthermore, this data captures foundational epigenetic details in two valuable porcine cell lines and contributes to the growing body of knowledge surrounding the epigenetic landscape in this species.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"16"},"PeriodicalIF":3.9,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077184","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}
引用次数: 0
Su(Hw) interacts with Combgap to establish long-range chromatin contacts. Su(Hw)与 Combgap 相互作用,建立长程染色质接触。
IF 3.9 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-05-21 DOI: 10.1186/s13072-024-00541-x
Nadezhda E Vorobyeva, Alexey N Krasnov, Maksim Erokhin, Darya Chetverina, Marina Mazina
{"title":"Su(Hw) interacts with Combgap to establish long-range chromatin contacts.","authors":"Nadezhda E Vorobyeva, Alexey N Krasnov, Maksim Erokhin, Darya Chetverina, Marina Mazina","doi":"10.1186/s13072-024-00541-x","DOIUrl":"10.1186/s13072-024-00541-x","url":null,"abstract":"<p><strong>Background: </strong>Insulator-binding proteins (IBPs) play a critical role in genome architecture by forming and maintaining contact domains. While the involvement of several IBPs in organising chromatin architecture in Drosophila has been described, the specific contribution of the Suppressor of Hairy wings (Su(Hw)) insulator-binding protein to genome topology remains unclear.</p><p><strong>Results: </strong>In this study, we provide evidence for the existence of long-range interactions between chromatin bound Su(Hw) and Combgap, which was first characterised as Polycomb response elements binding protein. Loss of Su(Hw) binding to chromatin results in the disappearance of Su(Hw)-Combgap long-range interactions and in a decrease in spatial self-interactions among a subset of Su(Hw)-bound genome sites. Our findings suggest that Su(Hw)-Combgap long-range interactions are associated with active chromatin rather than Polycomb-directed repression. Furthermore, we observe that the majority of transcription start sites that are down-regulated upon loss of Su(Hw) binding to chromatin are located within 2 kb of Combgap peaks and exhibit Su(Hw)-dependent changes in Combgap and transcriptional regulators' binding.</p><p><strong>Conclusions: </strong>This study demonstrates that Su(Hw) insulator binding protein can form long-range interactions with Combgap, Polycomb response elements binding protein, and that these interactions are associated with active chromatin factors rather than with Polycomb dependent repression.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"17"},"PeriodicalIF":3.9,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077188","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}
引用次数: 0
Roles of post-translational modifications of UHRF1 in cancer. UHRF1 的翻译后修饰在癌症中的作用。
IF 3.9 2区 生物学
Epigenetics & Chromatin Pub Date : 2024-05-09 DOI: 10.1186/s13072-024-00540-y
Lili Gu, Yongming Fu, Xiong Li
{"title":"Roles of post-translational modifications of UHRF1 in cancer.","authors":"Lili Gu, Yongming Fu, Xiong Li","doi":"10.1186/s13072-024-00540-y","DOIUrl":"10.1186/s13072-024-00540-y","url":null,"abstract":"<p><p>UHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"17 1","pages":"15"},"PeriodicalIF":3.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900024","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}
引用次数: 0
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