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

Panamarova, Maryna and Cox, Andy and Wicher, Krzysztof B. and Butler, Richard and Bulgakova, Natalia and Jeon, Shin and Rosen, Barry and Seong, Rho H. and Skarnes, William and Crabtree, Gerald and Zernicka-Goetz, Magdalena (2016) The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo. Development, 143 (8). pp. 1271-1283. ISSN 0950-1991. PMCID PMC4852518. doi:10.1242/dev.131961.

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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.

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Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2016. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received October 14, 2015. Accepted February 22, 2016. Published online April 19, 2016. We thank W. Xu for antibody against methylated BAF155; R. Kemler for Troma1 antibody; A. Surani for wt ESCs and TSCs; P. Almeida Coelho, S. Vuoristo and A. Hupalowska for technical assistance; M. Bredford for the Carm1−/− line; and 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 a Wellcome Trust Senior Fellowship [098287 to M.Z.-G.]; M.P. is supported by the Darwin Trust of Edinburgh. Deposited in PMC for immediate release. Author contributions: M.Z.-G. designed the study, developed the methodology and wrote the manuscript. M.P. designed the study, developed the methodology, collected the data, performed the analysis and wrote the manuscript. A.C. developed the methodology, collected the data and performed the analysis. K.W., S.J. and B.R. collected the data and performed the analysis. R.B. and N.B. performed the analysis. R.H.S., W.S. and G.C. wrote the manuscript. The authors declare no competing or financial interests.
Funding AgencyGrant Number
Wellcome Trust098287
Darwin Trust of EdinburghUNSPECIFIED
Subject Keywords:BAF complex, Chromatin remodelling, Epigenetics, Lineage specification, Mouse embryo, Pluripotency, SMARCC1
Issue or Number:8
PubMed Central ID:PMC4852518
Record Number:CaltechAUTHORS:20190405-170315353
Persistent URL:
Official Citation:The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo Maryna Panamarova, Andy Cox, Krzysztof B. Wicher, Richard Butler, Natalia Bulgakova, Shin Jeon, Barry Rosen, Rho H. Seong, William Skarnes, Gerald Crabtree, Magdalena Zernicka-Goetz Development 2016 143: 1271-1283; doi: 10.1242/dev.131961
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94540
Deposited By: George Porter
Deposited On:09 Apr 2019 20:41
Last Modified:16 Nov 2021 17:05

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