Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation

Diana Langer; Igor Martianov; Daniel Alpern; Muriel Rhinn; Céline Keime; Pascal Dollé; Gabrielle Mengus; Irwin Davidson

doi:10.1038/ncomms11063

Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation

Nat Commun. 2016 Mar 30:7:11063. doi: 10.1038/ncomms11063.

Authors

Diana Langer¹, Igor Martianov¹, Daniel Alpern^{1

2}, Muriel Rhinn³, Céline Keime¹, Pascal Dollé³, Gabrielle Mengus¹, Irwin Davidson¹

Affiliations

¹ 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.
² L'École polytechnique fédérale de Lausanne, Route Cantonale, 1015 Lausanne, Switzerland.
³ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Body Patterning / drug effects
Body Patterning / genetics
Cardiovascular Abnormalities / embryology
Cardiovascular Abnormalities / genetics
Cardiovascular Abnormalities / pathology
Cell Differentiation* / drug effects
Cell Differentiation* / genetics
Cell Survival / drug effects
Embryo Loss / genetics
Embryo Loss / pathology
Embryonic Development* / drug effects
Embryonic Development* / genetics
Female
Gene Expression Regulation, Developmental / drug effects
Germ Cells / drug effects
Germ Cells / metabolism
Mice
Mice, Inbred C57BL
Mouse Embryonic Stem Cells / drug effects
Mouse Embryonic Stem Cells / metabolism*
Mutation
Myocardial Contraction / drug effects
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / pathology
Neural Crest / drug effects
Neural Crest / pathology
Neurogenesis / drug effects
Neurogenesis / genetics
Neurons / drug effects
Neurons / metabolism
Phenotype
Pregnancy
Protein Subunits / genetics
Protein Subunits / metabolism*
Transcription Factor TFIID / deficiency
Transcription Factor TFIID / genetics
Transcription Factor TFIID / metabolism*
Tretinoin / pharmacology

Substances

Biomarkers
Protein Subunits
TAF4 protein, mouse
Transcription Factor TFIID
Tretinoin