{"title":"Chromatin-Based Control of Mammalian Sex Determination: Integrating Epigenetic and Metabolic Mechanisms.","authors":"Naoki Okashita, Makoto Tachibana","doi":"10.1007/978-981-92-1439-6_3","DOIUrl":null,"url":null,"abstract":"<p><p>Recent studies have demonstrated that mammalian sex determination is governed not only by trans-acting transcription factors but also by cis-acting chromatin modifications. This review summarizes recent advances in understanding how histone and DNA modifications contribute to sex determination, including the precise temporal regulation of the Y-linked testis-determining gene Sry. Key chromatin regulators-such as KDM3A, EHMT1/2, TET2, CBP/p300, KDM6B, CBX2, and CDYL-shape the chromatin landscape to promote male fate. We also highlight the emerging role of iron metabolism in modulating the activity of chromatin-modifying enzymes, thereby linking cellular metabolic state to epigenetic regulation. Together, these findings underscore the critical role of epigenetic fine-tuning in ensuring proper sex determination and may provide novel insights into the etiology of human disorders of sex development (DSDs).</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1517 ","pages":"27-36"},"PeriodicalIF":0.0000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in experimental medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/978-981-92-1439-6_3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Recent studies have demonstrated that mammalian sex determination is governed not only by trans-acting transcription factors but also by cis-acting chromatin modifications. This review summarizes recent advances in understanding how histone and DNA modifications contribute to sex determination, including the precise temporal regulation of the Y-linked testis-determining gene Sry. Key chromatin regulators-such as KDM3A, EHMT1/2, TET2, CBP/p300, KDM6B, CBX2, and CDYL-shape the chromatin landscape to promote male fate. We also highlight the emerging role of iron metabolism in modulating the activity of chromatin-modifying enzymes, thereby linking cellular metabolic state to epigenetic regulation. Together, these findings underscore the critical role of epigenetic fine-tuning in ensuring proper sex determination and may provide novel insights into the etiology of human disorders of sex development (DSDs).
期刊介绍：
Advances in Experimental Medicine and Biology provides a platform for scientific contributions in the main disciplines of the biomedicine and the life sciences. This series publishes thematic volumes on contemporary research in the areas of microbiology, immunology, neurosciences, biochemistry, biomedical engineering, genetics, physiology, and cancer research. Covering emerging topics and techniques in basic and clinical science, it brings together clinicians and researchers from various fields.
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