Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α)
Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α)
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DOI：
10.1093/emboj/17.23.6979
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发表时间：
1998-12-01
期刊：
影响因子：
11.4
通讯作者：
Yaniv, M
中科院分区：
文献类型：
--
作者：
Reyes, JC;Barra, J;Yaniv, M
哺乳动物SWI-SNF复合物是进化上保守的多亚基机器，参与转录激活过程中的染色质重塑。在这种复合物中，BRM（SNF 2 α）和BRG 1（SNF 2 β）蛋白是相互排斥的亚基，据信它们利用ATP水解的能量影响核小体结构。为了表征BRM和BRG 1功能的可能差异，并进一步了解含BRM的SWI-SNF复合物的作用，通过同源重组使小鼠BRM基因失活。BRM-/-小鼠发育正常，表明观察到的BRG 1蛋白的上调可以在突变细胞的SWI-SNF复合物中功能性地取代BRM。尽管如此，成年突变小鼠比对照同窝出生的小鼠重15%。这可能是由细胞增殖增加引起的，如在突变肝脏中检测到的更高的有丝分裂指数所证明的。这进一步得到以下观察结果的支持：突变胚胎成纤维细胞在响应细胞融合或DNA损伤时在细胞周期的G（0）/G（1）期停滞的能力显著缺陷。这些研究表明，BRM参与成年小鼠细胞增殖的调节。
The mammalian SWI-SNF complex is an evolutionarily conserved, multi-subunit machine, involved in chromatin remodelling during transcriptional activation. Within this complex, the BRM (SNF2 alpha) and BRG1 (SNF2 beta) proteins are mutually exclusive subunits that are believed to affect nucleosomal structures using the energy of ATP hydrolysis. In order to characterize possible differences in the function of BRM and BRG1, and to gain further insights into the role of BRM-containing SWI-SNF complexes, the mouse BRM gene was inactivated by homologous recombination. BRM-/- mice develop normally, suggesting that an observed up-regulation of the BRG1 protein can functionally replace BRM in the SWI-SNF complexes of mutant cells. Nonetheless, adult mutant mice were similar to 15% heavier than control littermates. This may be caused by increased cell proliferation, as demonstrated by a higher mitotic index detected in mutant livers. This is supported further by the observation that mutant embryonic fibroblasts were significantly deficient in their ability to arrest in the G(0)/G(1) phase of the cell cycle in response to cell confluency or DNA damage. These studies suggest that BRM participates in the regulation of cell proliferation in adult mice.