A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes
A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes
复制标题
DOI：
10.1016/s1097-2765(00)00127-1
复制
发表时间：
2000-12-01
期刊：
影响因子：
16
通讯作者：
Magnuson, T
中科院分区：
文献类型：
--
作者：
Bultman, S;Gebuhr, T;Magnuson, T
哺乳动物SWI/SNF复合体利用Brahma(BRM)或Brahma相关基因1(BRG1)催化亚基以ATP依赖的方式重塑核小体，以前的研究表明ARM是可有可无的，这表明ARM和BRG1在功能上是多余的。为了验证这一假设，我们通过基因打靶产生了BRG1零突变，令人惊讶的是，纯合子在围着床期死亡。此外，胚泡生长研究表明，内细胞团和滋养外胚层都不能存活。然而，用其他类型的细胞进行的实验表明，BRG1不是一个通用的细胞生存因素。此外，BRG1杂合子更容易发生脑外畸形和肿瘤。这些结果证明，生物化学相似的染色质重塑复合体在哺乳动物发育过程中具有截然不同的功能。
Mammalian SWI/SNF complexes utilize either brahma (Brm) or brahma-related gene 1 (Brg1) catalytic subunits to remodel nucleosomes in an ATP-dependent manner, arm was previously shown to be dispensable, suggesting that arm and Brg1 are functionally redundant. To test this hypothesis, we have generated a Brg1 null mutation by gene targeting, and, surprisingly, homozygotes die during the periimplantation stage. Furthermore, blastocyst outgrowth studies indicate that neither the inner cell mass nor trophectoderm survives. However, experiments with other cell types demonstrate that Brg1 is not a general cell survival factor. In addition, Brg1 heterozygotes are predisposed to exencephaly and tumors. These results provide evidence that biochemically similar chromatin-remodeling complexes have dramatically different functions during mammalian development.