The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo
Seong, Rho H
The Company of Biologists
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Panamarova, M., Cox, A., Wicher, K., Butler, R., Bulgakova, N., Jeon, S., Rosen, B., et al. (2016). The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo. Development, 143 1271-1283. https://doi.org/10.1242/dev.131961
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.
We are grateful to: W. Xu for an antibody against methylated BAF155; R. Kemler for an antibody against Troma1, A. Surani for TS cells, P. Almeida Coelho, S. Vuoristo and A. Hupalowska for technical assistance; M. Bredford for the CARM1 -/- line; D. Glover, M-E Torres-Padilla, P. P. Amaral, K. Miyamoto, A. Bruce, I. Bedzhov and J. Gurdon for helpful suggestions. This work was supported by The Wellcome Trust Senior Fellowship to MZG; M.P. is supported by the Darwin Trust of Edinburgh.
Biotechnology and Biological Sciences Research Council (BB/K00056X/1)
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External DOI: https://doi.org/10.1242/dev.131961
This record's URL: https://www.repository.cam.ac.uk/handle/1810/254062