Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening.

Abstract:

: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, Hnf1α 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.

journal_name

Cell Res

journal_title

Cell research

authors

Ji S,Zhu L,Gao Y,Zhang X,Yan Y,Cen J,Li R,Zeng R,Liao L,Hou C,Gao Y,Gao S,Wei G,Hui L

doi

10.1038/cr.2017.36

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

642-656

issue

5

eissn

1001-0602

issn

1748-7838

pii

cr201736

journal_volume

27

pub_type

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