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Auto-suppression of...
Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation
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- Zhang, Xiao-Jie (author)
- Univ Chinese Acad Sci, Peoples R China
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- Han, Bin-Bin (author)
- Univ Chinese Acad Sci, Peoples R China
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- Shao, Zhen-Yu (author)
- Univ Chinese Acad Sci, Peoples R China
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- Yan, Rui (author)
- Univ Chinese Acad Sci, Peoples R China; Beijing Inst Stem Cell & Regenerat Med, Peoples R China
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- Gao, Juan (author)
- Univ Chinese Acad Sci, Peoples R China
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- Liu, Ting (author)
- Univ Chinese Acad Sci, Peoples R China; Shanghai Tech Univ, Peoples R China
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- Jin, Zi-Yang (author)
- Univ Chinese Acad Sci, Peoples R China
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- Lai, Weiyi (author)
- Chinese Acad Sci, Peoples R China
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- Xu, Zhi-Mei (author)
- Univ Chinese Acad Sci, Peoples R China
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- Wang, Chao-Han (author)
- Univ Chinese Acad Sci, Peoples R China
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- Zhang, Fengjuan (author)
- Univ Chinese Acad Sci, Peoples R China
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- Gu, Chan (author)
- Changping Lab, Peoples R China
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- Wang, Yin (author)
- Chinese Acad Med Sci RU069, Peoples R China; Fudan Univ, Peoples R China
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- Wang, Hailin (author)
- Chinese Acad Sci, Peoples R China
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- Walsh, Colum (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Ulster Univ, North Ireland
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- Guo, Fan (author)
- Univ Chinese Acad Sci, Peoples R China; Beijing Inst Stem Cell & Regenerat Med, Peoples R China
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- Xu, Guo-Liang (author)
- Univ Chinese Acad Sci, Peoples R China; Chinese Acad Med Sci RU069, Peoples R China; Fudan Univ, Peoples R China
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- Du, Ya-Rui (author)
- Univ Chinese Acad Sci, Peoples R China
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(creator_code:org_t)
- NATURE PORTFOLIO, 2024
- 2024
- English.
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In: Nature Structural & Molecular Biology. - : NATURE PORTFOLIO. - 1545-9993 .- 1545-9985. ; 31:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development. Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhang, Xiao-Jie
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Han, Bin-Bin
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Shao, Zhen-Yu
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Yan, Rui
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Gao, Juan
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Liu, Ting
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Jin, Zi-Yang
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Lai, Weiyi
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Xu, Zhi-Mei
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Wang, Chao-Han
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Zhang, Fengjuan
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Gu, Chan
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Wang, Yin
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Wang, Hailin
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Walsh, Colum
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Guo, Fan
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Xu, Guo-Liang
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Du, Ya-Rui
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Nature Structura ...
- By the university
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Linköping University