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论文题目: Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility
英文论文题目: Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility
第一作者: Lio, CW; Zhang, JY; Gonzalez-Avalos, E; Hogan, PG; Chang, X; Rao, A
英文第一作者: Lio, CW; Zhang, JY; Gonzalez-Avalos, E; Hogan, PG; Chang, X; Rao, A
联系作者: Chang, X (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China.
英文联系作者: Chang, X (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China.
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发表年度: 2016
卷: 5
期:
页码: e18290
摘要: Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Ig kappa locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Ig kappa 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igx enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igx enhancer function by modulating the modification status of DNA.
英文摘要: Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Ig kappa locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Ig kappa 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igx enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igx enhancer function by modulating the modification status of DNA.
刊物名称: ELIFE
英文刊物名称: ELIFE
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学科: Biology
英文学科: Biology
影响因子: 7.725
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论文类别: Article
英文论文类别: Article
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