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TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors.

Abstract：

:Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1)-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity. 5hmC and HNF4A expression from P1 are dependent on ten-eleven translocation (TET) dioxygenases. In turn, the liver pioneer factor FOXA2 is necessary for TET1 binding to the P1 locus. Both FOXA2 and TETs are required for the 5hmC-related switch in HNF4A expression. The epigenetic event identified here may be a key step for the establishment of the hepatocyte program by HNF4A.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Ancey PB,Ecsedi S,Lambert MP,Talukdar FR,Cros MP,Glaise D,Narvaez DM,Chauvet V,Herceg Z,Corlu A,Hernandez-Vargas H

doi

10.1016/j.stemcr.2017.05.023

subject

Has Abstract

pub_date

2017-07-11 00:00:00

pages

264-278

issue

1

issn

2213-6711

pii

S2213-6711(17)30230-8

journal_volume

9

pub_type

杂志文章

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