Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Hota, Swetansu K.; Johnson, Jeffrey R.; Verschueren, Erik; Thomas, Reuben; Blotnick, Aaron M.; Zhu, Yiwen; Sun, Xin; Pennacchio, Len A.; Krogan, Nevan J.; Bruneau, Benoit G.

doi:10.1242/dev.174086

Title: Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Journal Article · Wed Feb 27 00:00:00 EST 2019 · Development (Cambridge)

DOI:https://doi.org/10.1242/dev.174086· OSTI ID:1581103

Hota, Swetansu K. ^[1]; Johnson, Jeffrey R. ^[2]; Verschueren, Erik ^[2]; Thomas, Reuben ^[3]; Blotnick, Aaron M. ^[1]; Zhu, Yiwen ^[4]; Sun, Xin ^[5]; Pennacchio, Len A. ^[4]; Krogan, Nevan J. ^[2];

^[6]

Gladstone Inst., San Francisco, CA (United States); Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA (United States)
Gladstone Inst., San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)
Gladstone Inst., San Francisco, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
Univ. of Oxford (United Kingdom)
Gladstone Inst., San Francisco, CA (United States); Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.

Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM-associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit gene Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunopurification with mass spectrometry, we have determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocyte (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60c and BAF170 modulate chromatin accessibility, to promote accessibility at activated genes while closing chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific sites. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1581103

Journal Information:: Development (Cambridge), Vol. 146, Issue 19; ISSN 0950-1991

Publisher:: Company of BiologistsCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 27 works

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