title: Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation.
abstract: TAF4 (TATA-binding protein-associated factor 4) and its paralogue TAF4b are components of the TFIID core module. We inactivated the murine Taf4a gene to address Taf4 function during embryogenesis. Here we show that Taf4a(-/-) embryos survive until E9.5 where primary germ layers and many embryonic structures are identified showing Taf4 is dispensable for their specification. In contrast, Taf4 is required for correct patterning of the trunk and anterior structures, ventral morphogenesis and proper heart positioning. Overlapping expression of Taf4a and Taf4b during embryogenesis suggests their redundancy at early stages. In agreement with this, Taf4a(-/-) embryonic stem cells (ESCs) are viable and comprise Taf4b-containing TFIID. Nevertheless, Taf4a(-/-) ESCs do not complete differentiation into glutamatergic neurons and cardiomyocytes in vitro due to impaired preinitiation complex formation at the promoters of critical differentiation genes. We define an essential role of a core TFIID TAF in differentiation events during mammalian embryogenesis.
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Langer
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Martianov
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.|L'École polytechnique fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0002-4023-9652
authors.initials: D
authors.lastname: Alpern
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rhinn
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Keime
authors.affiliation: Department of Development and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Mengus
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D018376:Cardiovascular Abnormalities / Q000196:embryology / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D020964:Embryo Loss / Q000235:genetics / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009432:Neural Crest / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D021122:Protein Subunits; C523528:TAF4 protein, mouse; D035362:Transcription Factor TFIID; D014212:Tretinoin