A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription
A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription
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DOI：
10.1093/emboj/cdg219
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发表时间：
2003-05-01
期刊：
影响因子：
11.4
通讯作者：
Wong, JM
中科院分区：
文献类型：
--
作者：
Huang, ZQ;Li, JW;Wong, JM
核受体(NRs)对染色质的转录激活需要多种辅助因子，包括CBP/p300、SWI/SNF和Mediator。NRS如何招募这些多重辅助因素尚不清楚。在这里，我们表明雄激素受体和甲状腺激素受体的激活与SRC家族成员p300、SWI/SNF和介体复合体的启动子靶向性有关。我们发现，SWI/SNF的募集导致染色质重塑和DNA拓扑结构的改变，并且SWI/SNF和p300组蛋白乙酸酶活性都是激素依赖激活所必需的。重要的是，我们证明了SWI/SNF和介体复合体都可以通过p300靶向染色质，而p300本身是通过与SRC共激活物相互作用来招募的。此外，CBP/p300的组蛋白乙酰化促进了SWI/SNF和Mediator的招募。因此，我们的数据表明，激活所需的多种辅因子并不都是通过它们与NRs的直接相互作用来招募的，并强调了辅因子-辅因子相互作用和组蛋白修饰在协调多种辅因子招募中的作用。
Transcriptional activation from chromatin by nuclear receptors (NRs) requires multiple cofactors including CBP/p300, SWI/SNF and Mediator. How NRs recruit these multiple cofactors is not clear. Here we show that activation by androgen receptor and thyroid hormone receptor is associated with the promoter targeting of SRC family members, p300, SWI/SNF and the Mediator complex. We show that recruitment of SWI/SNF leads to chromatin remodeling with altered DNA topology, and that both SWI/SNF and p300 histone acetylase activity are required for hormone-dependent activation. Importantly, we show that both the SWI/SNF and Mediator complexes can be targeted to chromatin by p300, which itself is recruited through interaction with SRC coactivators. Furthermore, histone acetylation by CBP/p300 facilitates the recruitment of SWI/SNF and Mediator. Thus, our data indicate that multiple cofactors required for activation are not all recruited through their direct interactions with NRs and underscore a role of cofactor-cofactor interaction and histone modification in coordinating the recruitment of multiple cofactors.