Discovery and structural studies of histone demethylases

The discovery and structural elucidation of histone demethylases represent a groundbreaking advancement in the field of epigenetics. Histone methylation, a critical chromatin modification, was long regarded as irreversible until the identification of histone demethylases overturned this paradigm. In...

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Main Authors: Longfei Peng, Xinze Li, Hao Yang, Haonan Chen, Yue Yang, Shunfeng Peng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Epigenetics and Epigenomics
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Online Access:https://www.frontiersin.org/articles/10.3389/freae.2025.1594400/full
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author Longfei Peng
Xinze Li
Hao Yang
Haonan Chen
Yue Yang
Shunfeng Peng
author_facet Longfei Peng
Xinze Li
Hao Yang
Haonan Chen
Yue Yang
Shunfeng Peng
author_sort Longfei Peng
collection DOAJ
description The discovery and structural elucidation of histone demethylases represent a groundbreaking advancement in the field of epigenetics. Histone methylation, a critical chromatin modification, was long regarded as irreversible until the identification of histone demethylases overturned this paradigm. In 2004, the discovery of the first histone demethylase, LSD1 (Lysine-Specific Demethylase 1), unveiled the dynamic regulatory mechanisms governing methylation modifications. Subsequent identification of the JmjC domain-containing demethylase family further expanded the diversity and functional repertoire of these enzymes. Structural biology studies have revealed the molecular mechanisms by which these enzymes remove methyl groups via oxidation or hydroxylation reactions, providing key insights into their substrate specificity and catalytic processes. This article will provide a concise overview of the discovery history, fundamental structures, and functional mechanisms of histone demethylases, summarize research progress on identified histone demethylases, and offer novel insights and offer novel insights and suggestions for fundamental research on sites where demethylases remain undiscovered.
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publishDate 2025-05-01
publisher Frontiers Media S.A.
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series Frontiers in Epigenetics and Epigenomics
spelling doaj-art-6fb80be75a9d4e5ebac651cd9b6a8d922025-08-20T02:17:05ZengFrontiers Media S.A.Frontiers in Epigenetics and Epigenomics2813-706X2025-05-01310.3389/freae.2025.15944001594400Discovery and structural studies of histone demethylasesLongfei Peng0Xinze Li1Hao Yang2Haonan Chen3Yue Yang4Shunfeng Peng5Department of Chemistry, College of Sciences, Shanghai University, Shanghai, ChinaLongevity and Aging Institute, The Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Chemistry, College of Sciences, Shanghai University, Shanghai, ChinaLongevity and Aging Institute, The Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Chemistry, College of Sciences, Shanghai University, Shanghai, ChinaLab Center, School of Electrical and Information Engineering, Anhui University of Technology, Ma’anshan, Anhui, ChinaThe discovery and structural elucidation of histone demethylases represent a groundbreaking advancement in the field of epigenetics. Histone methylation, a critical chromatin modification, was long regarded as irreversible until the identification of histone demethylases overturned this paradigm. In 2004, the discovery of the first histone demethylase, LSD1 (Lysine-Specific Demethylase 1), unveiled the dynamic regulatory mechanisms governing methylation modifications. Subsequent identification of the JmjC domain-containing demethylase family further expanded the diversity and functional repertoire of these enzymes. Structural biology studies have revealed the molecular mechanisms by which these enzymes remove methyl groups via oxidation or hydroxylation reactions, providing key insights into their substrate specificity and catalytic processes. This article will provide a concise overview of the discovery history, fundamental structures, and functional mechanisms of histone demethylases, summarize research progress on identified histone demethylases, and offer novel insights and offer novel insights and suggestions for fundamental research on sites where demethylases remain undiscovered.https://www.frontiersin.org/articles/10.3389/freae.2025.1594400/fullhistone demethylaseslysine demethylationargine demethylationstructureKDM family
spellingShingle Longfei Peng
Xinze Li
Hao Yang
Haonan Chen
Yue Yang
Shunfeng Peng
Discovery and structural studies of histone demethylases
Frontiers in Epigenetics and Epigenomics
histone demethylases
lysine demethylation
argine demethylation
structure
KDM family
title Discovery and structural studies of histone demethylases
title_full Discovery and structural studies of histone demethylases
title_fullStr Discovery and structural studies of histone demethylases
title_full_unstemmed Discovery and structural studies of histone demethylases
title_short Discovery and structural studies of histone demethylases
title_sort discovery and structural studies of histone demethylases
topic histone demethylases
lysine demethylation
argine demethylation
structure
KDM family
url https://www.frontiersin.org/articles/10.3389/freae.2025.1594400/full
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AT xinzeli discoveryandstructuralstudiesofhistonedemethylases
AT haoyang discoveryandstructuralstudiesofhistonedemethylases
AT haonanchen discoveryandstructuralstudiesofhistonedemethylases
AT yueyang discoveryandstructuralstudiesofhistonedemethylases
AT shunfengpeng discoveryandstructuralstudiesofhistonedemethylases