Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1
Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1
复制标题
DOI：
10.1101/gad.13.6.637
复制
发表时间：
1999-03-15
影响因子：
10.5
通讯作者：
Li, R
中科院分区：
文献类型：
--
作者：
Hu, YF;Hao, ZL;Li, R
越来越多的转录因子已被证明可以激活DNA复制。然而，其潜在机制仍有待阐明。在这里，它表明，当拴系到细胞复制起点，乳腺癌蛋白BRCA1的酸性转录激活结构域改变局部染色质结构，刺激染色体DNA复制。BRCA1中的癌症易感突变消除了转录激活，也阻止了染色质重塑和复制激活。染色质重塑甚至在没有功能性复制起点的情况下也会发生。因此，增加染色质可及性可能是转录因子用于促进多个核过程的重要机制。
An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes.