Epigenetics & Chromatin最新文献

{"title":"H3K4me3 regulates the transcription of RSPO3 in dermal papilla cells to influence hair follicle morphogenesis and development.","authors":"Zhenyu Zhong, Kangkang Bai, Zhihao Song, Mengxue Yang, Minghao Li, Shanhe Wang, Xin Wang","doi":"10.1186/s13072-025-00611-8","DOIUrl":"10.1186/s13072-025-00611-8","url":null,"abstract":"<p><p>Morphogenesis and development of hair follicle fundamentally depend on the interaction between the epidermis and dermis, with dermal papilla cells (DPCs) playing a critical role in these processes. H3K4me3, one of the key histone modifications, is essential for coordinating gene expression. However, the epigenetic modification profile of H3K4me3 in cashmere goat DPCs and its mechanism of action in hair follicle development remain unexplored. In this study, the apparent regulation map of H3K4me3 was drawn by CUT&Tag technology. DPCs were exogenously treated with the H3K4me3 inhibitor BCL-121 and the agonist PBIT. Functional experiment results showed that increasing H3K4me3 levels significantly enhanced the proliferation capacity of DPCs and promoted the expression of Wnt signaling pathway-related genes. Subsequently, the regulatory mechanism of H3K4me3 was explored, and the differentially expressed gene RSPO3 in the embryonic stage regulated by H3K4me3 was screened through CUT&Tag and RNA-seq correlation analysis. Functional studies demonstrated that RSPO3 could promote DPCs proliferation, inhibit apoptosis, and increase the expression of genes related to the Wnt signaling pathway. In summary, our findings indicated that H3K4me3 regulates the transcription of RSPO3 in DPCs, which would lay the foundation for the molecular mechanism of hair follicle development.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"52"},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800723","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":"Bromodomain proteins IBD1 and IBD2 link histone acetylation to SWR1- and INO80-mediated H2A.Z regulation in Tetrahymena.","authors":"Jyoti Garg, Alejandro Saettone, Syed Nabeel-Shah, Steven Dang, Abdul Hadi Khalid, Jérémy Loehr, Alexandra Petrova, James D Burns, Peter Karabatsos, Sherin Shibin, Suzanne Wahab, Sean D Taverna, Jack F Greenblatt, Jean-Philippe Lambert, Jeffrey Fillingham","doi":"10.1186/s13072-025-00614-5","DOIUrl":"10.1186/s13072-025-00614-5","url":null,"abstract":"<p><strong>Background: </strong>INO80 and SWR1 are evolutionarily related ATP-dependent chromatin remodeling complexes that regulate the chromatin occupancy of the histone variant H2A.Z, playing critical roles in transcriptional regulation, genome replication, and DNA repair. While the H2A.Z-related functions of INO80 and SWR1 are well characterized in budding yeast and metazoans, much less is known about their composition and chromatin-targeting mechanisms outside of the Opisthokonts. We previously found that a distinct bromodomain-containing protein, IBD1, is involved in multiple chromatin-related complexes, including the SWR1-complex, in the ciliate protozoan Tetrahymena thermophila.</p><p><strong>Results: </strong>Here, we report that a closely related bromodomain-containing protein, IBD2, functions as an acetyl lysine reader module within a putative INO80 complex. Through iterative proteomic analyses, we show that the Tetrahymena INO80 complex retains several conserved subunits found in its yeast and metazoan counterparts. In vitro binding assays reveal that recombinant IBD2 preferentially recognizes acetylated histone H3 tails. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) demonstrates that IBD2 is enriched near transcription start sites and promoter regions. Notably, the IBD1 and IBD2 genomic binding profiles strongly correlate with that of H2A.Z (Hv1), supporting their functional association with the SWRI- and INO80-complexes.</p><p><strong>Conclusions: </strong>Together, our findings support a model in which H2A.Z chromatin dynamics are modulated by SWR1- and INO80-complexes that are differentially recruited to chromatin via distinct bromodomain proteins that recognize specific histone acetylation marks.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"51"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790483","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":"Dynamic epigenomic landscape and gene regulatory networks during embryonic development in Pacific white shrimp (Litopenaeus vannamei) as revealed by histone modification profiling using CUT&Tag.","authors":"Jiale Shi, Zhangru Qi, Miaomiao Yin, Qifan Zeng, Jingjie Hu, Zhenmin Bao, Zhi Ye","doi":"10.1186/s13072-025-00615-4","DOIUrl":"10.1186/s13072-025-00615-4","url":null,"abstract":"<p><strong>Background: </strong>The Pacific white shrimp (Litopenaeus vannamei) is the most widely farmed shrimp species globally, yet the epigenetic regulation underlying its embryonic development remains largely unexplored. Histone modifications are known to orchestrate gene expression during early development in model organisms, but their role in crustaceans is poorly understood.</p><p><strong>Results: </strong>In this study, we present the first comprehensive histone modification landscape during L. vannamei embryogenesis using CUT&Tag (Cleavage Under Targets and Tagmentation). We profiled high-resolution landscapes of four histone marks (H3K4me1, H3K4me3, H3K27ac, H3K27me3) across seven developmental stages from blastula to nauplius, revealing dynamic chromatin state transitions associated with developmental progression. Integration with transcriptomic data uncovered a strong temporal correlation between chromatin states and gene expression, particularly during zygotic genome activation (ZGA). Furthermore, our analysis uncovered key developmental genes associated with critical biological processes such as molting, body segmentation, and neurogenesis, providing novel insights into the epigenetic regulation of these events. Functional annotation of cis-regulatory elements based on histone marks identified candidate enhancers and regulatory loci linked to these key genes.</p><p><strong>Conclusions: </strong>Our study provides the first epigenomic framework of shrimp embryogenesis, uncovering chromatin-based regulatory mechanisms during early development. The identification of stage-specific enhancers and active chromatin regions offers valuable resources for functional genomics in crustaceans and sheds light on conserved and divergent aspects of ZGA regulation beyond model systems.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"50"},"PeriodicalIF":3.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785780","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":"Identification of genetic and non-genetic modifiers of genomic imprinting through screening of imprinted DMR methylation in humans.","authors":"Francesco Cecere, Raissa Relator, Michael Levy, Ankit Verma, Haley McConkey, Bruno Hay Mele, Laura Pignata, Carlo Giaccari, Emilia D'Angelo, Subham Saha, Abu Saadat, Angela Sparago, Claudia Angelini, Flavia Cerrato, Bekim Sadikovic, Andrea Riccio","doi":"10.1186/s13072-025-00612-7","DOIUrl":"10.1186/s13072-025-00612-7","url":null,"abstract":"<p><strong>Background: </strong>Genomic imprinting is required for normal development, and abnormal methylation of differentially methylated regions (iDMRs) controlling the parent of origin-dependent expression of the imprinted genes has been found in congenital disorders affecting growth, metabolism, neurobehavior, and in cancer. In most of these cases the cause of the imprinting abnormalities is unknown. Also, these studies have generally been performed on a limited number of CpGs, and a systematic investigation of iDMR methylation in the general population is lacking.</p><p><strong>Results: </strong>By analysing a vast number of either in-house generated or online available whole-genome methylation array datasets of unaffected individuals, and patients with complex and rare disorders, we determined the most common iDMR methylation profiles in a large population and identified many genetic and non-genetic factors contributing to their variability in blood DNA. We found that methylation variability was not homogeneous within the iDMRs and that the CpGs closer to the ZFP57 binding sites are less susceptible to methylation changes. We demonstrated the methylation polymorphism of three iDMRs and the atypical behaviour of several others, and reported the association of 25 disease- and 47 non-disease-complex traits as well as 15 Mendelian and chromosomal disorders with iDMR methylation changes. The most significantly associated complex traits included ageing, intracytoplasmic sperm injection, African versus European ancestry, female sex, pre- and postnatal exposure to pollutants and blood cell type compositions, while the associated genetic diseases included Down syndrome and the developmental disorders with molecular defects in the DNA methyltransferases DNMT1 and DNMT3B, H3K36 methyltransferase SETD2, chromatin remodelers SRCAP and SMARCA4 and transcription factor ADNP.</p><p><strong>Conclusions: </strong>These findings identify several genetic and non-genetic factors including new genes associated with genomic imprinting maintenance in humans, which may have a role in the aetiology of the diseases with imprinting abnormalities and have clear implications in molecular diagnostics.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"47"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709692","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":"H2A.X N-terminal acetylation is a newly identified NAA40-mediated modification that is responsive to UV irradiation.","authors":"Ariel Klavaris, Costas Koufaris, Roberta Noberini, Maria Kouma, Christina Demetriadou, Alessandro Ghiringhelli, Nikolas Dietis, Tiziana Bonaldi, Antonis Kirmizis","doi":"10.1186/s13072-025-00608-3","DOIUrl":"10.1186/s13072-025-00608-3","url":null,"abstract":"<p><strong>Background: </strong>N-terminal acetylation (Nt-Ac), mediated by N-terminal acetyltransferases (NATs) is one of the most abundant protein modifications occurring approximately in 80% of all eukaryotic proteins. In contrast to the broad spectrum NATs, the human N-alpha-acetyltransferase 40 (NAA40) is highly specific, currently known to Nt-acetylate only the two histone proteins H4 and H2A, which share an Ser(1)-Gly(2)-Arg(3)-Gly(4) N-terminal sequence. Previous work from our lab and others has highlighted the biological and clinical relevance of this NAA40-mediated modification.</p><p><strong>Results: </strong>In this study, by performing in silico analysis of protein sequences combined with biochemical assays we identify the histone variants H2A.X and H2A.J and the chromatin remodeler SMARCD2 as new potential substrates of human NAA40. Subsequently, focusing on H2A.X, we show for the first time by mass spectrometry analysis that H2A.X is N-terminally acetylated (Nt-acH2A.X) within human cells. Next, we demonstrate that NAA40 specifically interacts and N-terminally acetylates histone H2A.X, in vitro and within cells. Finally, we provide evidence that H2A.X N-terminal acetylation is responsive to Ultraviolet B (UVB)-induced DNA damage and its associated enzyme NAA40 affects the survival of cells exposed to UVB irradiation.</p><p><strong>Conclusion: </strong>Our findings identify H2A.X as a novel bona fide substrate of NAA40. Moreover, the responsiveness of H2A.X N-terminal acetylation to UV-induced DNA damage indicates that this is a dynamic modification with potential biological functions.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"46"},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643990","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":"Improved epigenetic age prediction models by combining sex chromosome and autosomal markers.","authors":"Zhong Wan, Peter Henneman, Huub C J Hoefsloot, Ate D Kloosterman, Pernette J Verschure","doi":"10.1186/s13072-025-00606-5","DOIUrl":"10.1186/s13072-025-00606-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alterations in epigenetic DNA methylation (DNAm) can be used as an accurate and robust method for biological age prediction. We assessed the feasibility of incorporating sex chromosomal DNAm markers into a six autosomal DNAm CpG marker-based age prediction model, since DNAm-based prediction modeling has predominantly relied on analyzing DNAm patterns on autosomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We employed random forest regression (RFR) to construct age prediction models with publicly available DNAm Infinium 450 K microarray data of sex chromosomes from human whole blood and buffy coat samples and assessed the RFR model performance based on the root-mean squared error (RMSE) and the mean absolute deviation (MAD) of cross-validation. Four types of models were constructed consisting of DNAm probes on sex chromosomes only, on sex chromosomes and autosomes together, on sex chromosomes and/or autosomes with additional stratification by sex and/or age restriction, and reduced models comprising the top best performing sex chromosomal probes combined with six best performing autosomal probes from a previous study. Our data indicated no added predictive value of Y chromosomal DNAm markers in our best-performing prediction model, even though we acknowledged the potential of applying Y chromosomal markers for age prediction. Yet, a significantly improved accuracy of age prediction was observed using a restricted set of X chromosomal combined with the six best predicting autosomal DNAm probes. In this reduced model we noted an RMSE and MAD of 2.54 and 1.89 years, respectively. Particularly, four DNAm markers on the X chromosome exhibited a strong correlation with age, i.e., cg27064949 (DGAT2L6), cg04532200 (PLXNB3), cg01882566 (RPGR) and cg25140188 (annotated to an intergenic region).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our findings illustrate that an age prediction model built with a set of sex chromosomal markers combined with autosomal age-informative markers, may serve as a high accuracy model to predict chronological age and may be even competitive with commonly used model built with autosomal DNAm markers only. This study represents a step forward towards the application of epigenetic autosomal and sex chromosomal combined age prediction models for aging and forensic research. Highlights A set of age-prediction models based on DNA methylation (DNAm) markers on sex chromosomes and autosomes was constructed using random forest regression (RFR). From the total dataset containing 1291 whole blood and 547 buffy coat blood samples, 860 whole blood samples were used as training set and 481 as test set, while 365 buffy coat datasets were used as training set and 182 as test set. Cross-validation of the constructed RFR models using more than 10,000 X and 30 Y chromosomal DNAm markers from all collected blood samples, provided a root-mean squared error (RMSE) ranging from 7.70 to 14.29 years, and a mean absolute deviation (MAD) f","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"45"},"PeriodicalIF":4.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643991","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":"Epigenetic regulation of MED12: a key contributor to the leukemic chromatin landscape and transcriptional dysregulation.","authors":"Arundhati Chavan, Cassidy Jones, Whit Lawrence, Samrat Roy Choudhury","doi":"10.1186/s13072-025-00610-9","DOIUrl":"10.1186/s13072-025-00610-9","url":null,"abstract":"<p><strong>Background: </strong>MED12 is a key regulator of transcription and chromatin architecture, essential for normal hematopoiesis. While its dysregulation has been implicated in hematological malignancies, the mechanisms driving its upregulation in acute myeloid leukemia (AML) remain poorly understood. We investigated MED12 expression across AML subgroups by integrating chromatin accessibility profiling, histone modification landscapes, and DNA methylation (DNAm) patterns. Functional assays using DNMT inhibition were performed to dissect the underlying regulatory mechanisms.</p><p><strong>Results: </strong>MED12 shows subtype-specific upregulation in AML compared to hematopoietic stem and progenitor cells, independent of somatic mutations. Chromatin accessibility profiling reveals that the MED12 locus is epigenetically primed in AML blasts, with increased DNase hypersensitivity at regulatory elements. Histone modification analysis demonstrates strong H3K4me3 and H3K27ac enrichment around the transcription start site (TSS), consistent with promoter activation, while upstream and intragenic regions exhibit enhancer-associated marks (H3K4me1, H3K27ac). Notably, hypermethylation within TSS-proximal regulatory regions (TPRRs)-including promoter-overlapping and adjacent CpG islands-correlates with ectopic MED12 overexpression, challenging the canonical view of DNAm as strictly repressive. Functional studies show that DNMT inhibition via 5-azacytidine reduces MED12 expression despite promoter demethylation in cells with hypermethylated TPRRs, suggesting a noncanonical role for DNA methylation in maintaining active transcription. Furthermore, MED12 expression positively correlates with DNMT3A and DNMT3B expression, implicating these methyltransferases in sustaining its epigenetic activation.</p><p><strong>Conclusion: </strong>This study identifies a novel regulatory axis in which aberrant DNA methylation, rather than genetic mutation, drives MED12 upregulation in AML. Our findings suggest that TPRR hypermethylation may function noncanonically to support transcriptional activation, likely in cooperation with enhancer elements. These results underscore the importance of epigenetic mechanisms in AML and highlight enhancer-linked methylation as a potential contributor to oncogene dysregulation. Future studies should further explore the role of noncanonical methylation-mediated gene activation in AML pathogenesis and therapeutic targeting.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"44"},"PeriodicalIF":4.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638565","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":"Introduction of epigenetic variation contribute to resistance against the human parasite Schistosoma mansoni.","authors":"Nelia Luviano-Aparicio, Marie Lopez, Bart Haegeman, Pierick Mouginot, Cristian Chaparro, Paola B Arimondo, Benoit Pujol, Céline Cosseau, Christoph Grunau","doi":"10.1186/s13072-025-00607-4","DOIUrl":"10.1186/s13072-025-00607-4","url":null,"abstract":"","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"43"},"PeriodicalIF":4.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638566","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":"Molecular mechanisms and biological functions of active DNA demethylation in plants.","authors":"Ruixian Zhu, Yan Xue, Weiqiang Qian","doi":"10.1186/s13072-025-00605-6","DOIUrl":"10.1186/s13072-025-00605-6","url":null,"abstract":"<p><p>DNA methylation is a conserved epigenetic modification that plays important roles in silencing transposable elements, regulating gene expression, and maintaining genome stability. In plants, DNA methylation is de novo established by the RNA-directed DNA methylation pathway and maintained during each cell cycle. It can be actively removed by the REPRESSOR OF SILENCING 1/DEMETER family proteins through the base excision repair pathway. Active DNA demethylation is essential for plant growth, development, reproduction and stress adaptation. During the past two decades, significant progress has been made in our understanding of active DNA demethylation. In this review, we will discuss the molecular mechanisms, regulation, and biological functions of active DNA demethylation in plants.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"41"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568032","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 multitalented TIP60 chromatin remodeling complex: wearing many hats in epigenetic regulation, cell division and diseases.","authors":"Maria Virginia Santopietro, Diego Ferreri, Yuri Prozzillo, Patrizio Dimitri, Giovanni Messina","doi":"10.1186/s13072-025-00603-8","DOIUrl":"10.1186/s13072-025-00603-8","url":null,"abstract":"<p><p>The TIP60 complex is an evolutionarily conserved, multifunctional chromatin remodeling complex involved in critical cellular processes, including DNA repair, transcription regulation, and cell cycle control. Although its molecular organization and functions have been extensively studied, a comparative synthesis of its context-specific roles across evolutionarily distant species and pathological conditions is important to fully grasp its biological and clinical significance. In this review, we provide an integrative overview of the TIP60 complex, emphasizing its composition and conserved functions in Homo sapiens and Drosophila melanogaster, with comparative insights from plant systems. We explore how TIP60 complex dysregulation contributes to the molecular pathology of cancer and neurodevelopmental disorders, highlighting recent mechanistic insights. We also examine the emerging interplay between TIP60 complex subunits and long non-coding RNAs, which are increasingly recognized as pivotal regulators of genome accessibility and transcriptional programs. Finally, in this intriguing scenario, we highlight the non-canonical functions of the TIP60 complex in mitosis and cytokinesis, underscoring its moonlighting roles in maintaining genomic and cellular integrity, beyond its established contribution to epigenetic regulation. By connecting these diverse aspects, our review aims to provide an integrated perspective on the TIP60 complex and its expanding functional landscape in health and disease.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"40"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555526","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}