The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development

Abstract

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 embryonicα- 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.