Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14
Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14
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DOI：
10.1038/sj.emboj.7600143
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发表时间：
2004-03-24
期刊：
影响因子：
11.4
通讯作者：
Cairns, BR
中科院分区：
文献类型：
--
作者：
Kasten, M;Szerlong, H;Cairns, BR
染色质重构与染色质修饰的协调是基因调控中的一个中心话题。酵母染色质重塑复合物RSC具有多个溴结构域，用于乙酰基-赖氨酸和组蛋白尾部相互作用的基序。在这里，我们确定和表征Rsc 4，并表明它具有串联的必需溴结构域。条件rsc 4布罗莫结构域突变被分离，并且与gcn 5Delta组合是致命的，而与esa 1的组合生长良好。涉及组蛋白H3（Gcn 5的主要靶点）的Lys 14，而不是其他H3或H4赖氨酸残基的替换，也赋予rsc 4突变株严重的生长缺陷。重要的是，野生型Rsc 4结合在Lys 14处乙酰化的H3尾肽，而布罗莫结构域突变体衍生物则没有。特定组蛋白去乙酰化酶的缺失抑制了Rsc 4布罗莫结构域突变，表明Rsc 4促进基因活化。此外，rsc 4突变体在烟酸生物合成、细胞壁完整性和其他途径相关基因的激活方面表现出缺陷。综上所述，Rsc 4具有依赖于H3 Lys 14乙酰化以辅助RSC复合物进行基因活化的必需串联溴结构域。
The coordination of chromatin remodeling with chromatin modification is a central topic in gene regulation. The yeast chromatin remodeling complex RSC bears multiple bromodomains, motifs for acetyl-lysine and histone tail interaction. Here, we identify and characterize Rsc4 and show that it bears tandem essential bromodomains. Conditional rsc4 bromodomain mutations were isolated, and were lethal in combination with gcn5Delta, whereas combinations with esa1 grew well. Replacements involving Lys14 of histone H3 (the main target of Gcn5), but not other H3 or H4 lysine residues, also conferred severe growth defects to rsc4 mutant strains. Importantly, wild-type Rsc4 bound an H3 tail peptide acetylated at Lys14, whereas a bromodomain mutant derivative did not. Loss of particular histone deacetylases suppressed rsc4 bromodomain mutations, suggesting that Rsc4 promotes gene activation. Furthermore, rsc4 mutants displayed defects in the activation of genes involved in nicotinic acid biosynthesis, cell wall integrity, and other pathways. Taken together, Rsc4 bears essential tandem bromodomains that rely on H3 Lys14 acetylation to assist RSC complex for gene activation.