The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also required to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. These findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions. SUMMARY: The chromatin remodeling factor Brg1 is essential for mesoderm induction and, by modulating active and repressive chromatin states, is involved in promoting the activation of dynamic enhancers.
Brg1 modulates enhancer activation in mesoderm lineage commitment
Jeffrey M. Alexander,Swetansu K. Hota,Daniel He,Sean Thomas,Lena Ho,L. Pennacchio,B. Bruneau
Published 2015 in Development
ABSTRACT
PUBLICATION RECORD
- Publication year
2015
- Venue
Development
- Publication date
2015-04-15
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- brg1
A chromatin remodeling factor examined as a regulator of chromatin state during mesoderm lineage commitment.
- cardiomyocyte differentiation
The developmental process that generates heart muscle cells from precursor cells.
- distal enhancers
Enhancer elements located away from promoter-proximal regions that regulate gene expression over distance.
- enhancer activation
The transition of regulatory enhancer elements into an active state capable of supporting gene regulation.
- h3k27ac
Acetylation of histone H3 at lysine 27, a chromatin mark associated with active regulatory regions.
Aliases: H3K27 acetylation
- lineage-specific gene expression
A gene expression program characteristic of a particular developmental lineage.
- mesoderm induction
The differentiation program in which pluripotent cells are driven toward mesoderm identity.
- non-mesodermal developmental regulators
Developmental control genes associated with lineages outside the mesoderm program.
- polycomb complexes
Chromatin-associated repressive complexes that maintain silenced states at developmental genes.
Aliases: Polycomb
REFERENCES
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