Bultman S, Gebuhr T, Yee D, La Mantia C, Nicholson J, Gilliam A, Randazzo F, Metzger D, Chambon P, Crabtree G, Magnuson T
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
Mol Cell. 2000 Dec;6(6):1287-95. doi: 10.1016/s1097-2765(00)00127-1.
Mammalian SWI/SNF complexes utilize either brahma (Brm) or brahma-related gene 1 (Brg1) catalytic subunits to remodel nucleosomes in an ATP-dependent manner. Brm was previously shown to be dispensable, suggesting that Brm 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.
哺乳动物的SWI/SNF复合物利用婆罗门（Brm）或婆罗门相关基因1（Brg1）催化亚基以ATP依赖的方式重塑核小体。先前已证明Brm是可有可无的，这表明Brm和Brg1在功能上是冗余的。为了验证这一假设，我们通过基因靶向产生了Brg1无效突变，令人惊讶的是，纯合子在植入前阶段死亡。此外，囊胚生长研究表明，内细胞团和滋养外胚层均无法存活。然而，对其他细胞类型的实验表明，Brg1不是一般的细胞存活因子。此外，Brg1杂合子易患无脑畸形和肿瘤。这些结果证明，在哺乳动物发育过程中，生化性质相似的染色质重塑复合物具有截然不同的功能。
