Histone modifications influence mediator interactions with chromatin.
Histone modifications influence mediator interactions with chromatin.
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DOI：
10.1093/nar/gkr551
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发表时间：
2011-10
影响因子：
14.9
通讯作者：
Myers LC
中科院分区：
文献类型：
--
作者：
Zhu X;Zhang Y;Bjornsdottir G;Liu Z;Quan A;Costanzo M;Dávila López M;Westholm JO;Ronne H;Boone C;Gustafsson CM;Myers LC
中介复合体将DNA结合的转录因子的激活信号传递到核心转录机器。全基因组定位研究表明，介体占据不仅与高水平的转录相关，而且该复合体也存在于转录沉默的位置。我们提供的证据表明，Mediator的本地化是由与组蛋白尾巴的相互作用指导的，这种相互作用是由它们的翻译后修饰来调节的。一个定量的、高密度的遗传相互作用图揭示了介体成分和影响染色质结构的因素之间的联系，特别是组蛋白脱乙酰酶。多肽结合分析表明，纯野生型介体与组蛋白H3和H4的尾部形成稳定的络合物。这些结合分析还表明，组蛋白H4赖氨酸16的乙酰化特异性地抑制了介体-组蛋白H4肽的相互作用，组蛋白H4赖氨酸16是转录沉默的关键残基。最后，通过平铺阵列分析验证了这些发现，结果表明，介体与体内核小体的占有率存在广泛的相关性，但与组蛋白H4赖氨酸16处的核小体乙酰化呈负相关。我们的研究表明，染色质结构和组蛋白的乙酰化状态与介体的定位密切相关。
The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization.
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影响因子：
16
作者：
Altaf, Mohammed;Utley, Rhea T.;Cote, Jacques
通讯作者：
Cote, Jacques
影响因子：
10.5
作者：
Lariviere, Laurent;Seizl, Martin;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
4.8
作者：
Borggrefe, T;Davis, R;Kornberg, RD
通讯作者：
Kornberg, RD
影响因子：
5.3
作者：
Kim, JW;Iyer, VR
通讯作者：
Iyer, VR
影响因子：
14.9
作者：
Guglielmi, B;van Berkum, NL;Werner, M
通讯作者：
Werner, M