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 chromatinremodeling 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. :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.

BRG1 promotesCOUP-TFIIexpression and venous specification during embryonic vascular development

“…Therefore, one outstanding issue is whether BRG1 differentially impacts the timing and location of COUP-TFII expression in developing vasculature. This research article demonstrates that BRG1 promotes venous COUP-TFII expression during early stages of vascular development, but it is not clear whether BRG1 is required for COUP-TFII maintenance on more mature veins, as Brg1 fl/fl :Tie2-Cre + embryos die from anemia by E11.0 (Griffin et al, 2008). To address this issue, vascular Brg1 excision must be induced at later stages of embryonic development.…”

“…Tissues were fixed in a 2% PFA/0.2% glutaraldehyde solution, washed and X-gal stained as described (Griffin et al, 2008) for 48 hours at room temperature. The stained yolk sacs were dissected away from embryos and placentae and flat-mounted in DABCO mounting media on glass slides as described above.…”

ATP-dependent chromatin remodeling during mammalian development

“…For example, BAF complex subunits have specific and important roles in maintaining hematopoietic stem cells (HSCs), the stem cells that give rise to all cellular components of blood (Krasteva et al, 2012). They also control the differentiation of HSCs to different lineages (Bultman et al, 2005;Griffin et al, 2008;Vradii et al, 2006) and, subsequently, different stages of B-and Tcell development.…”

Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumor Growth Arrest and Multi-Lineage Differentiation of Malignant Rhabdoid Tumors

“…In particular, SMARCB1 is required in the SWI/SNF chromatin remodeling complex for controlling the differentiation potential of MRT cells (14)(15)(16). Furthermore, mounting evidence supports a role for SMARCB1 and functional chromatin remodeling complexes in cellular lineage commitment and differentiation, including myogenic (15,17), adipogenic (18), and erythropoietic (19) differentiation pathways.…”