Brg1 modulates enhancer activation in mesoderm lineage commitment

被引：84

作者：

Alexander, Jeffrey M. ^{[1
,2
]}

Hota, Swetansu K. ^{[1
,2
]}

He, Daniel ^{[1
,2
]}

Thomas, Sean ^{[1
,2
]}

Ho, Lena ^{[3
]}

Pennacchio, Len A. ^{[4
,5
]}

Bruneau, Benoit G. ^{[1
,2
,6
,7
]}

机构：

[1] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA

[2] Roddenberry Ctr Stem Cell Biol & Med Gladstone, San Francisco, CA 94158 USA

[3] ASTAR, Inst Med Biol, Singapore 138648, Singapore

[4] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA

[5] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA

[6] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA

来源：

DEVELOPMENT | 2015年 / 142卷 / 08期

关键词：

Chromatin; Enhancers; Gene expression; Histone modification; Mesoderm; Stem cells;

D O I：

10.1242/dev.109496

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

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 lineagespecific 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 Polycombmediated 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.

引用

页码：1418 / 1430

页数：13

共 53 条

[1]

Agalioti T., Lomvardas S., Parekh B., Yie J., Maniatis T., Thanos D., Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter, Cell, 103, pp. 667-678, (2000)

[2]

Attanasio C., Nord A.S., Zhu Y., Blow M.J., Biddie S.C., Mendenhall E.M., Dixon J., Wright C., Hosseini R., Akiyama J.A., Et al., Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis, Genome Res, 24, pp. 920-929, (2014)

[3]

Aulehla A., Pourquie O., Signaling gradients during paraxial mesoderm development, Cold Spring Harb. Perspect. Biol, 2, (2010)

[4]

Bultman S., Gebuhr T., Yee D., La Mantia C., Nicholson J., Gilliam A., Randazzo F., Metzger D., Chambon P., Crabtree G., Et al., A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/ SNF complexes, Mol. Cell, 6, pp. 1287-1295, (2000)

[5]

Bultman S.J., Gebuhr T.C., Magnuson T., A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development, Genes Dev, 19, pp. 2849-2861, (2005)

[6]

Cai W., Albini S., Wei K., Willems E., Guzzo R.M., Tsuda M., Giordani L., Spiering S., Kurian L., Yeo G.W., Et al., Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment, Genes Dev, 27, pp. 2332-2344, (2013)

[7]

Calo E., Wysocka J., Modification of enhancer chromatin: What, how, and why?, Mol. Cell, 49, pp. 825-837, (2013)

[8]

Carver E.A., Jiang R., Lan Y., Oram K.F., Gridley T., The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition, Mol. Cell. Biol, 21, pp. 8184-8188, (2001)

[9]

Chiriac A., Terzic A., Park S., Ikeda Y., Faustino R., Nelson T.J., SDF-1-enhanced cardiogenesis requires CXCR4 induction in pluripotent stem cells, J. Cardiovasc. Transl. Res, 3, pp. 674-682, (2010)

[10]

Ernst J., Kheradpour P., Mikkelsen T.S., Shoresh N., Ward L.D., Epstein C.B., Zhang X., Wang L., Issner R., Coyne M., Et al., Mapping and analysis of chromatin state dynamics in nine human cell types, Nature, 473, pp. 43-49, (2011)

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