The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo
| Autor: | Magdalena Zernicka-Goetz, Barry Rosen, William C. Skarnes, Maryna Panamarova, Shin Jeon, Natalia A. Bulgakova, Rho Hyun Seong, Gerald R. Crabtree, Krzysztof B. Wicher, Andy Cox, Richard Butler |
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| Přispěvatelé: | Butler, Richard [0000-0002-3885-1332], Zernicka-Goetz, Magdalena [0000-0002-7004-2471], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Pluripotency
Male 0301 basic medicine Homeobox protein NANOG Protein-Arginine N-Methyltransferases CARM1 Embryonic Development Gene Expression Chromatin remodelling Biology Mouse embryo Methylation Epigenesis Genetic Lineage specification Mice 03 medical and health sciences Downregulation and upregulation Gene expression Animals Humans Cell Lineage Epigenetics BAF complex Molecular Biology Transcription factor Genetics Gene Expression Regulation Developmental SMARCC1 Stem Cells and Regeneration Chromatin Assembly and Disassembly Embryonic stem cell Cell biology Mice Inbred C57BL Blastocyst 030104 developmental biology Mice Inbred CBA Female Ectopic expression Transcription Factors Developmental Biology |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 0950-1991 |
| Popis: | 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. Summary: Associations of BAF155 with other BAF complex subunits are enriched in extra-embryonic lineages prior to implantation, while changes in BAF155 levels modulate the expression of early developmental markers. |
| Databáze: | OpenAIRE |
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