Griffin Courtney T, Brennan Jennifer, Magnuson Terry
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Development. 2008 Feb;135(3):493-500. doi: 10.1242/dev.010090. Epub 2007 Dec 19.
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.
ATP 依赖性染色质重塑复合物有助于哺乳动物胚胎中基因表达呈现适当的时空模式，因此在许多发育过程中发挥重要作用。SWI/SNF 样染色质重塑复合物使用两种不同的 ATP 酶之一作为其催化亚基：婆罗门（BRM，也称为 SMARCA2）和婆罗门相关基因 1（BRG1，也称为 SMARCA4）。我们使用 Tie2-Cre 转基因有条件地删除了一个 floxed Brg1 等位基因，该转基因在发育中的造血和内皮细胞中表达。Brg1(fl/fl):Tie2-Cre(+)胚胎在妊娠中期死于贫血，因为突变的原始红细胞无法转录胚胎α和β珠蛋白，随后发生凋亡。此外，Brg1(fl/fl):Tie2-Cre(+)胚胎中外胚层卵黄囊的血管重塑异常。重要的是，Brm 缺陷不会加剧 Brg1(fl/fl):Tie2-Cre(+)胚胎中发现的红细胞生成或血管异常，这意味着含 Brg1 的 SWI/SNF 样复合物而非含 Brm 的复合物在原始红细胞生成和早期血管发育中起关键作用。
