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

Development. 2008 Feb;135(3):493-500. doi: 10.1242/dev.010090. Epub 2007 Dec 19.

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. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blood Cells / cytology
  • Blood Vessels / abnormalities
  • Blood Vessels / embryology*
  • Blood Vessels / enzymology*
  • Blood Vessels / ultrastructure
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Embryo Loss
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / pathology
  • Embryo, Mammalian / ultrastructure
  • Embryonic Development
  • Erythroblasts / cytology
  • Erythroblasts / metabolism
  • Erythropoiesis / physiology*
  • Gene Expression Regulation, Developmental
  • Globins / genetics
  • Integrases / metabolism
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptor, TIE-2 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Yolk Sac / abnormalities
  • Yolk Sac / pathology
  • Yolk Sac / ultrastructure

Substances

  • Nuclear Proteins
  • Transcription Factors
  • Globins
  • Receptor, TIE-2
  • Cre recombinase
  • Integrases
  • Smarca4 protein, mouse
  • DNA Helicases