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论文题目: Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening
英文论文题目: Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening
第一作者: Ji, SY; Zhu, LY; Gao, YM; Zhang, XR; Yan, YP; Cen, J; Li, RX; Zeng, R; Liao, LJ; Hou, CH; Gao, YW; Gao, SR; Wei, G; Hui, LJ
英文第一作者: Ji, SY; Zhu, LY; Gao, YM; Zhang, XR; Yan, YP; Cen, J; Li, RX; Zeng, R; Liao, LJ; Hou, CH; Gao, YW; Gao, SR; Wei, G; Hui, LJ
联系作者: Wei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China.
英文联系作者: Wei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 27
期: 5
页码: 642-656
摘要: Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1 alpha and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion. By characterizing the early molecular events during hepatic conversion, we found that Baf60b, a member of the SWI/SNF chromatin remodeling complex, links chromatin opening to ATM activation by facilitating ATM recruitment to the open chromatin regions of a panel of hepatic gene loci. These findings shed light on cellular responses to lineage conversion by revealing a function of the ATM-p53 pathway in sensing chromatin opening.
英文摘要: Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1 alpha and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion. By characterizing the early molecular events during hepatic conversion, we found that Baf60b, a member of the SWI/SNF chromatin remodeling complex, links chromatin opening to ATM activation by facilitating ATM recruitment to the open chromatin regions of a panel of hepatic gene loci. These findings shed light on cellular responses to lineage conversion by revealing a function of the ATM-p53 pathway in sensing chromatin opening.
刊物名称: CELL RESEARCH
英文刊物名称: CELL RESEARCH
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 15.606
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论文类别: Article
英文论文类别: Article
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