Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53
Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53
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DOI：
10.1016/j.cell.2004.05.009
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发表时间：
2004-06-11
期刊：
影响因子：
64.5
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
An, W;Kim, J;Roeder, RG
转录辅激活因子，修改组蛋白代表了一个越来越重要的组的调节因子，虽然他们的能力，修改其他因素，以及排除了共同的假设，他们必须采取行动组蛋白修饰。在先前研究的扩展中，显示了乙酰转移酶p300/CBP在p53功能中的作用，我们使用了用重组染色质模板和（共）激活剂重建的系统来证明（1）蛋白质精氨酸甲基转移酶PRMT 1和CARM 1在p53功能中的额外参与;（2）p300、PRMT 1和CARM 1的独立和有序合作功能;和（3）涉及与p53直接相互作用的机制，最重要的是，相应组蛋白底物的强制性修饰。ChIP分析已经证实了这些（和其他）共激活因子和同源组蛋白修饰在异位p53表达和/或UV照射后GADD 45基因上的有序积累。因此，这些研究定义了不同的辅因子功能，以及涉及不同的组蛋白修饰的潜在机制，在p53依赖性基因激活。
Transcriptional coactivators that modify histones represent an increasingly important group of regulatory factors, although their ability to modify other factors as well precludes common assumptions that they necessarily act by histone modification. In an extension of previous studies showing a role for acetyltransferase p300/CBP in p53 function, we have used systems reconstituted with recombinant chromatin templates and (co)activators to demonstrate (1) the additional involvement of protein arginine methyltransferases PRMT1 and CARM1 in p53 function; (2) both independent and ordered cooperative functions of p300, PRMT1, and CARM1; and (3) mechanisms that involve direct interactions with p53 and, most importantly, obligatory modifications of corresponding histone substrates. ChIP analyses have confirmed the ordered accumulation of these (and other) coactivators and cognate histone modifications on the GADD45 gene following ectopic p53 expression and/or UV irradiation. These studies thus define diverse cofactor functions, as well as underlying mechanisms involving distinct histone modifications, in p53-dependent gene activation.