title: The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo.
abstract: Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complex in vivo and regulates lineage specification of the mouse blastocyst. We find that associations of BAF155 with other BAF complex subunits become enriched in extra-embryonic lineages just prior to implantation. This enrichment is attributed to decreased mobility of BAF155 in extra-embryonic compared with embryonic lineages. Downregulation of BAF155 leads to increased expression of the pluripotency marker Nanog and its ectopic expression in extra-embryonic lineages, whereas upregulation of BAF155 leads to the upregulation of differentiation markers. Finally, we show that the arginine methyltransferase CARM1 methylates BAF155, which differentially influences assembly of the BAF complex between the lineages and the expression of pluripotency markers. Together, our results indicate a novel role of BAF-dependent chromatin remodelling in mouse development via regulation of lineage specification.
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Maryna
authors.initials: M
authors.lastname: Panamarova
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Cox
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Krzysztof B
authors.initials: KB
authors.lastname: Wicher
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Butler
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK Bateson Centre and Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bulgakova
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-747, South Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-747, South Korea.
authors.forename: Rho H
authors.initials: RH
authors.lastname: Seong
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: William
authors.initials: W
authors.lastname: Skarnes
authors.affiliation: Department of Developmental Biology, Stanford University Medical School, Stanford, CA 94305, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Crabtree
authors.affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK mz205@cam.ac.uk.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D019070:Cell Lineage / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C491090:Smarcc1 protein, mouse; D014157:Transcription Factors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: BAF complex; Chromatin remodelling; Epigenetics; Lineage specification; Mouse embryo; Pluripotency; SMARCC1