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Elife. 2014 Sep 10;3:e03613. doi: 10.7554/eLife.03613.

TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.

Author information

1
Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
2
Laboratoire TAGC, Aix-Marseille Université, UMR1090, Marseille, France.
3
Department of Integrated Structural Biology, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.

Abstract

The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. In this study, we describe a novel function of TAFs in directing genomic occupancy of a transcriptional activator. Using liver-specific inactivation in mice, we show that the TAF4 subunit of TFIID is required for post-natal hepatocyte maturation. TAF4 promotes pre-initiation complex (PIC) formation at post-natal expressed liver function genes and down-regulates a subset of embryonic expressed genes by increased RNA polymerase II pausing. The TAF4-TAF12 heterodimer interacts directly with HNF4A and in vivo TAF4 is necessary to maintain HNF4A-directed embryonic gene expression at post-natal stages and promotes HNF4A occupancy of functional cis-regulatory elements adjacent to the transcription start sites of post-natal expressed genes. Stable HNF4A occupancy of these regulatory elements requires TAF4-dependent PIC formation highlighting that these are mutually dependent events. Local promoter-proximal HNF4A-TFIID interactions therefore act as instructive signals for post-natal hepatocyte differentiation.

KEYWORDS:

biochemistry; bioinformatics; chromosomes; developmental biology; genes; genomics; mouse

PMID:
25209997
PMCID:
PMC4359380
DOI:
10.7554/eLife.03613
[Indexed for MEDLINE]
Free PMC Article

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