title: 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.
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Daniil
authors.initials: D
authors.lastname: Alpern
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Langer
authors.affiliation: Laboratoire TAGC, Aix-Marseille Université, UMR1090, Marseille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ballester
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Le Gras
authors.affiliation: Department of Integrated Structural Biology, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Romier
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Mengus
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication; D002454:Cell Differentiation / Q000235:genetics*; D002779:Cholestasis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D016678:Genome; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D007003:Hypoglycemia / Q000150:complications / Q000473:pathology; D051379:Mice; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000172:deficiency / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D018398:Homeodomain Proteins; D021122:Protein Subunits; C523528:TAF4 protein, mouse; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; C532029:Taf3 protein, mouse; D035362:Transcription Factor TFIID; D012319:RNA Polymerase II
keywords: biochemistry; bioinformatics; chromosomes; developmental biology; genes; genomics; mouse