Epigenetics & Chromatin最新文献

{"title":"Var∣Decrypt: a novel and user-friendly tool to explore and prioritize variants in whole-exome sequencing data.","authors":"Mohammad Salma,&nbsp;Elina Alaterre,&nbsp;Jérôme Moreaux,&nbsp;Eric Soler","doi":"10.1186/s13072-023-00497-4","DOIUrl":"https://doi.org/10.1186/s13072-023-00497-4","url":null,"abstract":"<p><strong>Background: </strong>High-throughput sequencing (HTS) offers unprecedented opportunities for the discovery of causative gene variants in multiple human disorders including cancers, and has revolutionized clinical diagnostics. However, despite more than a decade of use of HTS-based assays, extracting relevant functional information from whole-exome sequencing (WES) data remains challenging, especially for non-specialists lacking in-depth bioinformatic skills.</p><p><strong>Results: </strong>To address this limitation, we developed Var∣Decrypt, a web-based tool designed to greatly facilitate WES data browsing and analysis. Var∣Decrypt offers a wide range of gene and variant filtering possibilities, clustering and enrichment tools, providing an efficient way to derive patient-specific functional information and to prioritize gene variants for functional analyses. We applied Var∣Decrypt on WES datasets of 10 acute erythroid leukemia patients, a rare and aggressive form of leukemia, and recovered known disease oncogenes in addition to novel putative drivers. We additionally validated the performance of Var∣Decrypt using an independent dataset of ~ 90 multiple myeloma WES, recapitulating the identified deregulated genes and pathways, showing the general applicability and versatility of Var∣Decrypt for WES analysis.</p><p><strong>Conclusion: </strong>Despite years of use of WES in human health for diagnosis and discovery of disease drivers, WES data analysis still remains a complex task requiring advanced bioinformatic skills. In that context, there is a need for user-friendly all-in-one dedicated tools for data analysis, to allow biologists and clinicians to extract relevant biological information from patient datasets. Here, we provide Var∣Decrypt (trial version accessible here: https://vardecrypt.com/app/vardecrypt ), a simple and intuitive Rshiny application created to fill this gap. Source code and detailed user tutorial are available at https://gitlab.com/mohammadsalma/vardecrypt .</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670305","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":"Correction: Characterizing chromatin interactions of regulatory elements and nucleosome positions, using Hi‑C, Micro‑C, and promoter capture Micro‑C.","authors":"Beoung Hun Lee,&nbsp;Zexun Wu,&nbsp;Suhn K Rhie","doi":"10.1186/s13072-023-00498-3","DOIUrl":"https://doi.org/10.1186/s13072-023-00498-3","url":null,"abstract":"","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954531","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":"Strong interactions between highly dynamic lamina-associated domains and the nuclear envelope stabilize the 3D architecture of Drosophila interphase chromatin.","authors":"Igor S Tolokh, Nicholas Allen Kinney, Igor V Sharakhov, Alexey V Onufriev","doi":"10.1186/s13072-023-00492-9","DOIUrl":"10.1186/s13072-023-00492-9","url":null,"abstract":"<p><strong>Background: </strong>Interactions among topologically associating domains (TADs), and between the nuclear envelope (NE) and lamina-associated domains (LADs) are expected to shape various aspects of three-dimensional (3D) chromatin structure and dynamics; however, relevant genome-wide experiments that may provide statistically significant conclusions remain difficult.</p><p><strong>Results: </strong>We have developed a coarse-grained dynamical model of D. melanogaster nuclei at TAD resolution that explicitly accounts for four distinct epigenetic classes of TADs and LAD-NE interactions. The model is parameterized to reproduce the experimental Hi-C map of the wild type (WT) nuclei; it describes time evolution of the chromatin over the G1 phase of the interphase. The simulations include an ensemble of nuclei, corresponding to the experimentally observed set of several possible mutual arrangements of chromosomal arms. The model is validated against multiple structural features of chromatin from several different experiments not used in model development. Predicted positioning of all LADs at the NE is highly dynamic-the same LAD can attach, detach and move far away from the NE multiple times during interphase. The probabilities of LADs to be in contact with the NE vary by an order of magnitude, despite all having the same affinity to the NE in the model. These probabilities are mostly determined by a highly variable local linear density of LADs along the genome, which also has the same strong effect on the predicted positioning of individual TADs -- higher probability of a TAD to be near NE is largely determined by a higher linear density of LADs surrounding this TAD. The distribution of LADs along the chromosome chains plays a notable role in maintaining a non-random average global structure of chromatin. Relatively high affinity of LADs to the NE in the WT nuclei substantially reduces sensitivity of the global radial chromatin distribution to variations in the strength of TAD-TAD interactions compared to the lamin depleted nuclei, where a small (0.5 kT) increase of cross-type TAD-TAD interactions doubles the chromatin density in the central nucleus region.</p><p><strong>Conclusions: </strong>A dynamical model of the entire fruit fly genome makes multiple genome-wide predictions of biological interest. The distribution of LADs along the chromatin chains affects their probabilities to be in contact with the NE and radial positioning of highly mobile TADs, playing a notable role in creating a non-random average global structure of the chromatin. We conjecture that an important role of attractive LAD-NE interactions is to stabilize global chromatin structure against inevitable cell-to-cell variations in TAD-TAD interactions.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10350898","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":"CpG DNA methylation changes during epididymal sperm maturation in bulls.","authors":"Emanuele Capra,&nbsp;F Turri,&nbsp;B Lazzari,&nbsp;S Biffani,&nbsp;A Lange Consiglio,&nbsp;P Ajmone Marsan,&nbsp;A Stella,&nbsp;F Pizzi","doi":"10.1186/s13072-023-00495-6","DOIUrl":"https://doi.org/10.1186/s13072-023-00495-6","url":null,"abstract":"<p><strong>Background: </strong>During epididymal transit spermatozoa acquire specific morphological features which enhance their ability to swim in a progressive manner and interact with the oocytes. At the same time, sperm cells undergo specific molecular rearrangements essential for the fertilizing sperm to drive a correct embryo development. To assess epigenetic sperm changes during epididymal maturation, the caput, corpus and cauda epididymis sperm tracts were isolated from eight bulls and characterized for different sperm quality parameters and for CpG DNA methylation using Reduced Representation Bisulfite Sequencing (RRBS) able to identify differentially methylated regions (DMRs) in higher CpG density regions.</p><p><strong>Results: </strong>Caput sperm showed significant variation in motility and sperm kinetics variables, whereas spermatozoa collected from the corpus presented morphology variation and significant alterations in variables related to acrosome integrity. A total of 57,583 methylated regions were identified across the eight bulls, showing a significantly diverse distribution for sperm collected in the three epididymal regions. Differential methylation was observed between caput vs corpus (n = 11,434), corpus vs cauda (n = 12,372) and caput vs cauda (n = 2790). During epididymal transit a high proportion of the epigenome was remodeled, showing several regions in which methylation decreases from caput to corpus and increases from corpus to cauda.</p><p><strong>Conclusions: </strong>Specific CpG DNA methylation changes in sperm isolated from the caput, corpus, and cauda epididymis tracts are likely to refine the sperm epigenome during sperm maturation, potentially impacting sperm fertilization ability and spatial organization of the genome during early embryo development.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10228035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561459","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":"Premature ovarian insufficiency is associated with global alterations in the regulatory landscape and gene expression in balanced X-autosome translocations.","authors":"Adriana Di-Battista,&nbsp;Bianca Pereira Favilla,&nbsp;Malú Zamariolli,&nbsp;Natália Nunes,&nbsp;Alexandre Defelicibus,&nbsp;Lucia Armelin-Correa,&nbsp;Israel Tojal da Silva,&nbsp;Alexandre Reymond,&nbsp;Mariana Moyses-Oliveira,&nbsp;Maria Isabel Melaragno","doi":"10.1186/s13072-023-00493-8","DOIUrl":"https://doi.org/10.1186/s13072-023-00493-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with balanced X-autosome translocations and premature ovarian insufficiency (POI) constitute an interesting paradigm to study the effect of chromosome repositioning. Their breakpoints are clustered within cytobands Xq13-Xq21, 80% of them in Xq21, and usually, no gene disruption can be associated with POI phenotype. As deletions within Xq21 do not cause POI, and since different breakpoints and translocations with different autosomes lead to this same gonadal phenotype, a \"position effect\" is hypothesized as a possible mechanism underlying POI pathogenesis.</p><p><strong>Objective and methods: </strong>To study the effect of the balanced X-autosome translocations that result in POI, we fine-mapped the breakpoints in six patients with POI and balanced X-autosome translocations and addressed gene expression and chromatin accessibility changes in four of them.</p><p><strong>Results: </strong>We observed differential expression in 85 coding genes, associated with protein regulation, multicellular regulation, integrin signaling, and immune response pathways, and 120 differential peaks for the three interrogated histone marks, most of which were mapped in high-activity chromatin state regions. The integrative analysis between transcriptome and chromatin data pointed to 12 peaks mapped less than 2 Mb from 11 differentially expressed genes in genomic regions not related to the patients' chromosomal rearrangement, suggesting that translocations have broad effects on the chromatin structure.</p><p><strong>Conclusion: </strong>Since a wide impact on gene regulation was observed in patients, our results observed in this study support the hypothesis of position effect as a pathogenic mechanism for premature ovarian insufficiency associated with X-autosome translocations. This work emphasizes the relevance of chromatin changes in structural variation, since it advances our knowledge of the impact of perturbations in the regulatory landscape within interphase nuclei, resulting in the position effect pathogenicity.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517806","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":"The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.","authors":"Eva Monte-Serrano, Patricia Morejón-García, Ignacio Campillo-Marcos, Aurora Campos-Díaz, Elena Navarro-Carrasco, Pedro A Lazo","doi":"10.1186/s13072-023-00494-7","DOIUrl":"10.1186/s13072-023-00494-7","url":null,"abstract":"<p><strong>Background: </strong>Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be coordinated, a role that may be mediated by chromatin kinases such as VRK1, which phosphorylates histones H3 and H2A.</p><p><strong>Methods: </strong>The effect of VRK1 depletion and VRK1 inhibitor, VRK-IN-1, on the acetylation and methylation of histone H3 in K4, K9 and K27 was determined under different conditions, arrested or proliferating cells, in A549 lung adenocarcinoma and U2OS osteosarcoma cells.</p><p><strong>Results: </strong>Chromatin organization is determined by the phosphorylation pattern of histones mediated by different types of enzymes. We have studied how the VRK1 chromatin kinase can alter the epigenetic posttranslational modifications of histones by using siRNA, a specific inhibitor of this kinase (VRK-IN-1), and of histone acetyl and methyl transferases, as well as histone deacetylase and demethylase. Loss of VRK1 implicated a switch in the state of H3K9 posttranslational modifications. VRK1 depletion/inhibition causes a loss of H3K9 acetylation and facilitates its methylation. This effect is similar to that of the KAT inhibitor C646, and to KDM inhibitors as iadademstat (ORY-1001) or JMJD2 inhibitor. Alternatively, HDAC inhibitors (selisistat, panobinostat, vorinostat) and KMT inhibitors (tazemetostat, chaetocin) have the opposite effect of VRK1 depletion or inhibition, and cause increase of H3K9ac and a decrease of H3K9me3. VRK1 stably interacts with members of these four enzyme families. However, VRK1 can only play a role on these epigenetic modifications by indirect mechanisms in which these epigenetic enzymes are likely targets to be regulated and coordinated by VRK1.</p><p><strong>Conclusions: </strong>The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation in lysines 4, 9 and 27. VRK1 is a master regulator of chromatin organization associated with its specific functions, such as transcription or DNA repair.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9525964","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":"Loss of CpG island immunity to DNA methylation induced by mutation.","authors":"Bernhard Horsthemke,&nbsp;Adrian Bird","doi":"10.1186/s13072-023-00488-5","DOIUrl":"https://doi.org/10.1186/s13072-023-00488-5","url":null,"abstract":"<p><p>The inheritance of acquired traits in mammals is a highly controversial topic in biology. Recently, Takahashi et al. (Cell 186:715-731, 2023) have reported that insertion of CpG-free DNA into a CpG island (CGI) can induce DNA methylation of the CGI and that this aberrant methylation pattern can be transmitted across generations, even after removal of the foreign DNA. These results were interpreted as evidence for transgenerational inheritance of acquired DNA methylation patterns. Here, we discuss several interpretational issues raised by this study and consider alternative explanations.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9525053","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":"The MMP-2 histone H3 N-terminal tail protease is selectively targeted to the transcription start sites of active genes.","authors":"Benjamin H Weekley, Judd C Rice","doi":"10.1186/s13072-023-00491-w","DOIUrl":"10.1186/s13072-023-00491-w","url":null,"abstract":"<p><strong>Background: </strong>Proteolysis of the histone H3 N-terminal tail (H3NT) is an evolutionarily conserved epigenomic feature of nearly all eukaryotes, generating a cleaved H3 product that is retained in ~ 5-10% of the genome. Although H3NT proteolysis within chromatin was first reported over 60 years ago, the genomic sites targeted for H3NT proteolysis and the impact of this histone modification on chromatin structure and function remain largely unknown. The goal of this study was to identify the specific regions targeted for H3NT proteolysis and investigate the consequence of H3NT \"clipping\" on local histone post-translational modification (PTM) dynamics.</p><p><strong>Results: </strong>Leveraging recent findings that matrix metalloproteinase 2 (MMP-2) functions as the principal nuclear H3NT protease in the human U2OS osteosarcoma cell line, a ChIP-Seq approach was used to map MMP-2 localization genome wide. The results indicate that MMP-2 is selectively targeted to the transcription start sites (TSSs) of protein coding genes, primarily at the + 1 nucleosome. MMP-2 localization was exclusive to highly expressed genes, further supporting a functional role for H3NT proteolysis in transcriptional regulation. MMP-2 dependent H3NT proteolysis at the TSSs of these genes resulted in a > twofold reduction of activation-associated histone H3 PTMs, including H3K4me3, H3K9ac and H3K18ac. One of genes requiring MMP-2 mediated H3NT proteolysis for proficient expression was the lysosomal cathepsin B protease (CTSB), which we discovered functions as a secondary nuclear H3NT protease in U2OS cells.</p><p><strong>Conclusions: </strong>This study revealed that the MMP-2 H3NT protease is selectively targeted to the TSSs of active protein coding genes in U2OS cells. The resulting H3NT proteolysis directly alters local histone H3 PTM patterns at TSSs, which likely functions to regulate transcription. MMP-2 mediated H3NT proteolysis directly activates CTSB, a secondary H3NT protease that generates additional cleaved H3 products within chromatin.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9523494","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":"Caf1 regulates the histone methyltransferase activity of Ash1 by sensing unmodified histone H3.","authors":"Eojin Yoon,&nbsp;Ji-Joon Song","doi":"10.1186/s13072-023-00487-6","DOIUrl":"https://doi.org/10.1186/s13072-023-00487-6","url":null,"abstract":"<p><p>Histone modifications are one of the many key mechanisms that regulate gene expression. Ash1 is a histone H3K36 methyltransferase and is involved in gene activation. Ash1 forms a large complex with Mrg15 and Caf1/p55/Nurf55/RbAp48 (AMC complex). The Ash1 subunit alone exhibits very low activity due to the autoinhibition, and the binding of Mrg15 releases the autoinhibition. Caf1 is a scaffolding protein commonly found in several chromatin modifying complexes and has two histone binding pockets: one for H3 and the other for H4. Caf1 has the ability to sense unmodified histone H3K4 residues using the H3 binding pocket. However, the role of Caf1 in the AMC complex has not been investigated. Here, we dissected the interaction among the AMC complex subunits, revealing that Caf1 uses the histone H4 binding pocket to interact with Ash1 near the histone binding module cluster. Furthermore, we showed that H3K4 methylation inhibits AMC HMTase activity via Caf1 sensing unmodified histone H3K4 to regulate the activity in an internucleosomal manner, suggesting that crosstalk between H3K4 and H3K36 methylation. Our work revealed a delicate mechanism by which the AMC histone H3K36 methyltransferase complex is regulated.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455750","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":"Partial erosion on under-methylated regions and chromatin reprogramming contribute to oncogene activation in IDH mutant gliomas.","authors":"Xinyu Wang,&nbsp;Lijun Dai,&nbsp;Yang Liu,&nbsp;Chenghao Li,&nbsp;Dandan Fan,&nbsp;Yue Zhou,&nbsp;Pengcheng Li,&nbsp;Qingran Kong,&nbsp;Jianzhong Su","doi":"10.1186/s13072-023-00490-x","DOIUrl":"https://doi.org/10.1186/s13072-023-00490-x","url":null,"abstract":"<p><strong>Background: </strong>IDH1/2 hotspot mutations are well known to drive oncogenic mutations in gliomas and are well-defined in the WHO 2021 classification of central nervous system tumors. Specifically, IDH mutations lead to aberrant hypermethylation of under-methylated regions (UMRs) in normal tissues through the disruption of TET enzymes. However, the chromatin reprogramming and transcriptional changes induced by IDH-related hypermethylation in gliomas remain unclear.</p><p><strong>Results: </strong>Here, we have developed a precise computational framework based on Hidden Markov Model to identify altered methylation states of UMRs at single-base resolution. By applying this framework to whole-genome bisulfite sequencing data from 75 normal brain tissues and 15 IDH mutant glioma tissues, we identified two distinct types of hypermethylated UMRs in IDH mutant gliomas. We named them partially hypermethylated UMRs (phUMRs) and fully hypermethylated UMRs (fhUMRs), respectively. We found that the phUMRs and fhUMRs exhibit distinct genomic features and chromatin states. Genes related to fhUMRs were more likely to be repressed in IDH mutant gliomas. In contrast, genes related to phUMRs were prone to be up-regulated in IDH mutant gliomas. Such activation of phUMR genes is associated with the accumulation of active H3K4me3 and the loss of H3K27me3, as well as H3K36me3 accumulation in gene bodies to maintain gene expression stability. In summary, partial erosion on UMRs was accompanied by locus-specific changes in key chromatin marks, which may contribute to oncogene activation.</p><p><strong>Conclusions: </strong>Our study provides a computational strategy for precise decoding of methylation encroachment patterns in IDH mutant gliomas, revealing potential mechanistic insights into chromatin reprogramming that contribute to oncogenesis.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455749","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}