HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail.

HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail.
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DOI:
10.1016/j.molcel.2009.01.007
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发表时间:
2009-01-30
期刊:
影响因子:
16
通讯作者:
Cote, Jacques
Cote, Jacques
中科院分区:
生物学1区
文献类型:
--
作者:
Saksouk, Nehme;Avvakumov, Nikita;Champagne, Karen S.;Hung, Tiffany;Doyon, Yannick;Cayrou, Christelle;Paquet, Eric;Ullah, Mukta;Landry, Anne-Julie;Cote, Valrie;Yang, Xiang-Jiao;Gozani, Or;Kutateladze, Tatiana G.;Cote, Jacques

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HBO1 HAT蛋白是体内组蛋白H4乙酰化的主要来源,已被证明在基因调控和DNA复制中发挥关键作用。HBO1 HAT复合物的一个显著特征是在两个不同的亚基中存在三个PHD指结构域:肿瘤抑制蛋白ING4/5和JADE1/2/3。生化和功能分析表明,这些结构域与组蛋白H3 n端尾区相互作用,但对其甲基化状态具有不同的特异性。它们的组合作用在调节染色质结合和HBO1复合物的底物特异性以及细胞生长中是必不可少的。重要的是,对人类基因组的定位分析表明,HBO1复合物在整个基因编码区域富集,支持转录伸长的作用。这些结果强调了PHD指结构域在调节单个蛋白质复合体内染色质关联和组蛋白修饰串扰中的重要性和多功能性。
The HBO1 HAT protein is the major source of histone H4 acetylation in vivo and has been shown to play critical roles in gene regulation and DNA replication. A distinctive characteristic of HBO1 HAT complexes is the presence of three PHD finger domains in two different subunits: tumor suppressor proteins ING4/5 and JADE1/2/3. Biochemical and functional analyses indicate that these domains interact with histone H3 N-terminal tail region, but with a different specificity towards its methylation status. Their combinatorial action is essential in regulating chromatin binding and substrate specificity of HBO1 complexes, as well as cell growth. Importantly, localization analyses on the human genome indicate that HBO1 complexes are enriched throughout the coding regions of genes, supporting a role in transcription elongation. These results underline the importance and versatility of PHD finger domains in regulating chromatin association and histone modification cross-talk within a single protein complex.
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