{"title":"The histone code at a crossroads: history, context, and new approaches.","authors":"Julie Jung, Michael S Werner","doi":"10.1016/j.tig.2025.09.003","DOIUrl":null,"url":null,"abstract":"<p><p>Recent studies have reported that catalytically dead histone-modifying enzymes can rescue the function of their null alleles. Histone 'replacement' experiments have similarly found a lack of phenotypes for some modifications. Do these findings foretell a paradigm shift for the histone code hypothesis? Here, we discuss these results through the lens of ecology, evolution, and development ('eco-evo-devo') to provide context. We then highlight recent 'top-down' approaches, which start from environmentally influenced phenotypes and then attempt to identify causal mechanisms; placing function before molecule. Using this strategy, recent work in invertebrates has found key roles for histone acetylation and small RNAs in developmental plasticity. The synthesis of traditional 'bottom-up' with new 'top-down' approaches can resolve which molecules are epiphenomenal and which are truly epigenetic.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":16.3000,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tig.2025.09.003","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Recent studies have reported that catalytically dead histone-modifying enzymes can rescue the function of their null alleles. Histone 'replacement' experiments have similarly found a lack of phenotypes for some modifications. Do these findings foretell a paradigm shift for the histone code hypothesis? Here, we discuss these results through the lens of ecology, evolution, and development ('eco-evo-devo') to provide context. We then highlight recent 'top-down' approaches, which start from environmentally influenced phenotypes and then attempt to identify causal mechanisms; placing function before molecule. Using this strategy, recent work in invertebrates has found key roles for histone acetylation and small RNAs in developmental plasticity. The synthesis of traditional 'bottom-up' with new 'top-down' approaches can resolve which molecules are epiphenomenal and which are truly epigenetic.
期刊介绍：
Launched in 1985, Trends in Genetics swiftly established itself as a "must-read" for geneticists, offering concise, accessible articles covering a spectrum of topics from developmental biology to evolution. This reputation endures, making TiG a cherished resource in the genetic research community. While evolving with the field, the journal now embraces new areas like genomics, epigenetics, and computational genetics, alongside its continued coverage of traditional subjects such as transcriptional regulation, population genetics, and chromosome biology.
Despite expanding its scope, the core objective of TiG remains steadfast: to furnish researchers and students with high-quality, innovative reviews, commentaries, and discussions, fostering an appreciation for advances in genetic research. Each issue of TiG presents lively and up-to-date Reviews and Opinions, alongside shorter articles like Science & Society and Spotlight pieces. Invited from leading researchers, Reviews objectively chronicle recent developments, Opinions provide a forum for debate and hypothesis, and shorter articles explore the intersection of genetics with science and policy, as well as emerging ideas in the field. All articles undergo rigorous peer-review.
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