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