The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development.
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. Brg1(fl/fl):Tie2-Cre(+) embryos die at midgestation from anemia, as mutant primitive erythrocytes fail to transcribe embryonic alpha- and beta-globins, and subsequently undergo apoptosis. Additionally, vascular remodeling of the extraembryonic yolk sac is abnormal in Brg1(fl/fl):Tie2-Cre(+) embryos. Importantly, Brm deficiency does not exacerbate the erythropoietic or vascular abnormalities found in Brg1(fl/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.
Griffin
Courtney T
CT
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Brennan
Jennifer
J
Magnuson
Terry
T
D000818:Animals; D017209:Apoptosis; D001773:Blood Cells / Q000166:cytology; D001808:Blood Vessels / Q000002:abnormalities / Q000196:embryology* / Q000201:enzymology* / Q000648:ultrastructure; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D047108:Embryonic Development; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015017:Yolk Sac / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure
D009687:Nuclear Proteins; D014157:Transcription Factors; D005914:Globins; D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases