title: Embryonic stem cell differentiation requires full length Chd1.
abstract: The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1(Δ2/Δ2) mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.
authors.affiliation: Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Paolo
authors.initials: P
authors.lastname: Piatti
authors.affiliation: Epithelial Epigenetics and Development Laboratory, Institute of Medical Biology, A*Star, Singapore.
authors.forename: Chin Yan
authors.initials: CY
authors.lastname: Lim
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Austria.
authors.forename: Roxana
authors.initials: R
authors.lastname: Nat
authors.affiliation: Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Villunger
authors.affiliation: Division of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Geley
authors.affiliation: Epithelial Epigenetics and Development Laboratory, Institute of Medical Biology, A*Star, Singapore.
authors.forename: Yan Ting
authors.initials: YT
authors.lastname: Shue
authors.affiliation: Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Soratroi
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.affiliation: Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lusser
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D047108:Embryonic Development; D053595:Embryonic Stem Cells; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D012694:Serine / Q000235:genetics
chemical_list: C489844:Chd1 protein, mouse; D004268:DNA-Binding Proteins; D012694:Serine