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Published in

The Company of Biologists, Development, 2016

DOI: 10.1242/dev.131961

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BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Dynamic control of gene expression is essential for 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 the 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 a 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 to embryonic lineage. Down-regulation of BAF155 leads to increased expression of the pluripotency marker Nanog and its ectopic expression in extra-embryonic lineages, whereas up-regulation of BAF155 leads to up-regulation of differentiation markers. Finally, we show that arginine methyltransferase CARM1 methylates BAF155, which influences assembly of the BAF complex between the lineages and expression of pluripotency markers. Together our results indicate a novel role of BAF-dependent chromatin remodelling in mouse development via regulation of lineage specification.