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First published online 19 December 2007
doi: 10.1242/dev.010090

Development 135, 493-500 (2008)
Published by The Company of Biologists 2008
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The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development

Courtney T. Griffin, Jennifer Brennan and Terry Magnuson*

Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

* Author for correspondence (e-mail: terry_magnuson{at}med.unc.edu)

Accepted 1 November 2007

ATP-dependent chromatin-remodeling complexes contribute to the proper temporal and spatial patterns of gene expression in mammalian embryos and therefore play important roles in a number of developmental processes. SWI/SNF-like chromatin-remodeling complexes use one of two different ATPases as their catalytic subunit: brahma (BRM, also known as SMARCA2) and brahma-related gene 1 (BRG1, also known as SMARCA4). We have conditionally deleted a floxed Brg1 allele with a Tie2-Cre transgene, which is expressed in developing hematopoietic and endothelial cells. Brg1fl/fl:Tie2-Cre+ embryos die at midgestation from anemia, as mutant primitive erythrocytes fail to transcribe embryonic {alpha}- and β-globins, and subsequently undergo apoptosis. Additionally, vascular remodeling of the extraembryonic yolk sac is abnormal in Brg1fl/fl:Tie2-Cre+ embryos. Importantly, Brm deficiency does not exacerbate the erythropoietic or vascular abnormalities found in Brg1fl/fl:Tie2-Cre+ embryos, implying that Brg1-containing SWI/SNF-like complexes, rather than Brm-containing complexes, play a crucial role in primitive erythropoiesis and in early vascular development.

Key words: SWI/SNF, Brg1, Tie2-Cre, Erythropoiesis, β-globin, Vascular remodeling, Angiogenesis


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