A transcriptional switch mediated by cofactor methylation
A transcriptional switch mediated by cofactor methylation
复制标题
DOI：
10.1126/science.1065961
复制
发表时间：
2001-12-21
期刊：
影响因子：
56.9
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Xu, W;Chen, HW;Evans, RM
我们描述了一种基于核小体和转录辅助因子CREB结合蛋白(CBP)/p300受控甲基化的分子开关。CBP/p300甲基化位点定位于精氨酸残基，这是稳定KIX结构域结构所必需的，KIX结构域介导CREB招募。辅活化子相关的精氨酸甲基转移酶1(CARM1)通过阻断KIX与CREB的KID之间的相互作用来阻断CREB的激活。因此，CARM1通过其甲基转移酶的活性在环磷酸腺苷信号通路中起辅阻遏物的作用，同时也是核激素的辅活化子。这些结果在体内和体外提供了强有力的证据，证明组蛋白甲基化在激素诱导的基因激活中起关键作用，并将辅因子甲基化定义为激素信号转导中的一种新的调节机制。
We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/ p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyl-transferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.