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

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.
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https://hal.archives-ouvertes.fr/hal-01404987
Contributor : Benoit Ballester <>
Submitted on : Tuesday, February 6, 2018 - 3:20:51 PM
Last modification on : Monday, December 21, 2020 - 3:36:05 PM
Long-term archiving on: : Tuesday, May 8, 2018 - 7:09:26 AM

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Daniil Alpern, Diana Langer, Benoit Ballester, Stephanie Le Gras, Christophe Romier, et al.. TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation. eLife, eLife Sciences Publication, 2014, 3, pp.308-312. ⟨10.7554/eLife.03613.001⟩. ⟨hal-01404987⟩

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