Epigenetics & Chromatin最新文献

{"title":"Insulator BEAF32 regulates expression of tissue-specific genes and piRNA source loci in Drosophila ovaries.","authors":"Anastasia A Kobelyatskaya, Valeria Morgunova, Aleksey Kalinkin, Anna A Shchukina, Olesya Sokolova, Dmitry A Kwon, Sergei Funikov, Alla Kalmykova","doi":"10.1186/s13072-025-00613-6","DOIUrl":"10.1186/s13072-025-00613-6","url":null,"abstract":"<p><strong>Background: </strong>Insulators are the multifunctional DNA binding proteins that perform architectural functions and regulate gene transcription. Although insulators have a well-established role in genome organization, it is still unclear how insulator proteins affect the control of tissue-specific processes. The Drosophila insulator BEAF32 (Boundary Element-Associated Factor of 32 kD) is a component of chromatin complexes found in open chromatin regions containing promoters of housekeeping genes. BEAF32 knockout impairs oogenesis and female fertility suggesting its specific functions during oogenesis.</p><p><strong>Results: </strong>To get a better understanding of BEAF32 roles in oogenesis, we first examined its ovarian binding targets and discovered an enrichment of its localization sites in the promoters of both housekeeping and tissue-specific genes. Differential expression gene analysis revealed that BEAF32 knockout resulted in abnormal activation of non-ovarian tissue-specific genes in the ovaries, implying that BEAF32 regulates tissue-specific patterns of gene expression. We discovered that BEAF32 occupied many ovary-specific gene promoters and acted as a positive regulator of expression for the cell-cycle regulatory kinase, Polo. To investigate the possible role of BEAF32 in the Piwi-interacting RNAs (piRNAs) pathway we analyzed ovarian small RNAs in BEAF32 null mutants and found a strong decrease in the production of piRNAs from the 3R subtelomeric region. Our data suggest that the BEAF32-containing chromatin complex located upstream of the subtelomeric repeats preserves transcriptional and chromatin integrity of this domain in the germline. BEAF32 was also found to localize upstream of flamenco, a major piRNA source locus in follicular cells, and to be required for cell-specific transcription of the flamenco locus.</p><p><strong>Conclusions: </strong>Our findings suggest that BEAF32 coordinates multiple transcriptional regulatory functions important for Drosophila oogenesis. BEAF32 represses the ectopic expression of developmental and tissue-specific genes in the ovaries. BEAF32 regulates polo kinase and other oogenesis-related genes. We demonstrate here that BEAF32 play a specific ovarian role in the maintenance of piRNA-producing loci. Our results support an important role for the BEAF32 insulator protein in determining the proper landscape of tissue-specific gene expression.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"49"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734923","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":"Histone H4 lysine 20 methylation marks genes dynamically regulated during erythroid maturation.","authors":"Kristin Murphy, Michael Getman, Xiurui Lv, Zachary Murphy, Deanna Abid, Nabil Rahman, Michael Bulger, Laurie Steiner","doi":"10.1186/s13072-025-00609-2","DOIUrl":"10.1186/s13072-025-00609-2","url":null,"abstract":"<p><strong>Background: </strong>Methylation of H4K20 has been implicated in the regulation of gene expression but also plays essential roles in numerous cellular functions, making studies of its effects on transcription challenging. To gain insights into the role of H4K20 methylation in regulating gene expression, we studied H4K20me1 and H4K20me3 in the context of the well-characterized erythroid differentiation of human hematopoietic stem and progenitor cells.</p><p><strong>Results: </strong>H4K20me1 enrichment over the gene body was strongly correlated with expression changes. During erythroid differentiation, there was a dramatic decline in the level of RNA Polymerase II (Pol II); H4K20me1 was lost where Pol II was lost, and gained at genes where Pol II occupancy was maintained and transcripts were upregulated. We did identify a small subset of highly expressed genes, including beta-globin, that had a dramatic loss of H4K20me1 during erythroid differentiation, despite a substantial gain of Pol II. The histone demethylase PHF8 was present at these genes, as well as at the transcription start site of many active genes. In contrast to H4K20me1 over gene bodies correlating with transcription, enrichment at the transcription start site occurred at genes with low levels of Pol II occupancy and RNA expression throughout erythroid differentiation. The majority of H4K20me3 was present over intergenic regions, consistent with its well-established role as a repressor of repetitive elements. Intriguingly, H4K20me3 was also present at the transcription start site of genes with H4K20me1 over the gene body. At these genes, H4K20me3 levels were highly correlated with chromatin accessibility at the transcription start site, and an elevated Pol II pausing index. There was a dramatic loss of H4K20me3 occupancy in genic, but not intergenic, regions during erythroid differentiation.</p><p><strong>Conclusions: </strong>There are dynamic changes in H4K20 methylation during cellular differentiation that correlate strongly with Pol II occupancy and activity. These changes occurred in genic regions, with H4K20me3 at the transcription start site correlated with Pol II pausing, and H4K20me1 gene body levels tightly linked with transcriptional changes. Together, these data provide important insights into the role of H4K20 methylation in the regulation of gene expression during cellular differentiation.</p>","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"48"},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718959","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":"Correction: Artificial intelligence in cancer epigenomics: a review on advances in pan-cancer detection and precision medicine.","authors":"Karishma Sahoo, Prakash Lingasamy, Masuma Khatun, Sajitha Lulu Sudhakaran, Andres Salumets, Vino Sundararajan, Vijayachitra Modhukur","doi":"10.1186/s13072-025-00604-7","DOIUrl":"10.1186/s13072-025-00604-7","url":null,"abstract":"","PeriodicalId":49253,"journal":{"name":"Epigenetics & Chromatin","volume":"18 1","pages":"42"},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621000","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}