1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation

  1. Daniil Alpern
  2. Diana Langer
  3. Benoit Ballester
  4. Stephanie Le Gras
  5. Christophe Romier
  6. Gabrielle Mengus
  7. Irwin Davidson  Is a corresponding author
  1. Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, France
  2. Aix-Marseille Université, UMR1090 TAGC, France
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Cite this article as: eLife 2014;3:e03613 doi: 10.7554/eLife.03613

Abstract

The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. Here 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.

Article and author information

Author details

  1. Daniil Alpern

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Diana Langer

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Benoit Ballester

    Aix-Marseille Université, UMR1090 TAGC, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephanie Le Gras

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Ilkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Christophe Romier

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Ilkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Gabrielle Mengus

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Ilkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Irwin Davidson

    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France
    For correspondence
    irwin@igbmc.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animal Experiments were performed in compliance with National Animal Care Guidelines (European Commission directive 86/609/CEE; French decree no.87-848).

Reviewing Editor

  1. Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States

Publication history

  1. Received: June 6, 2014
  2. Accepted: September 9, 2014
  3. Accepted Manuscript published: September 10, 2014 (version 1)
  4. Version of Record published: October 3, 2014 (version 2)

Copyright

© 2014, Alpern et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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