Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes
Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes
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DOI：
10.1074/jbc.275.15.11514
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发表时间：
2000-04-14
影响因子：
4.8
通讯作者：
Bustin, M
中科院分区：
文献类型：
--
作者：
Bergel, M;Herrera, JE;Bustin, M
组蛋白的可逆乙酰化与染色质纤维的结构改变有关，从而影响各种 DNA 相关活动。在这里，我们证明组蛋白乙酰转移酶 p300 特异性乙酰化 HMG-14，这是一种与核小体结合并降低染色质纤维紧密度的非组蛋白结构蛋白。我们鉴定了 7 个主要的乙酰化位点，其中 6 个是新的，并且在 HMG-14 或密切相关的 HMG-17 蛋白中尚未被乙酰化。所有乙酰化位点均涉及进化上保守的残基：3 个位于 HMG-14/-17 核小体结合结构域内，4 个位于蛋白质的二分核定位结构域内或附近。在组织培养细胞中，乙酰化模式表示选择性过程，其中 HMG-14 的亚组分优先被乙酰化。我们发现核小体结合域是体内乙酰化的主要靶点，p300 对 HMG-14 的特异性乙酰化削弱了其与核小体核心的相互作用。我们的结果表明 p300 调节 HMG-14 与核小体的相互作用。因此，p300 可能不仅通过修饰组蛋白或转录因子，而且还通过靶向结构非组蛋白来影响染色质相关活性。
The reversible acetylation of histones is associated with structural alterations in the chromatin fiber that affect various DNA-related activities. Here we show that the histone acetyltransferase p300 specifically acetylates HMG-14, a nonhistone structural protein that binds to nucleosomes and reduces the compactness of the chromatin fiber. We identify 7 major acetylation sites, 6 of which are novel and have not been known to be acetylated in either HMG-14 or the closely related HMG-17 protein. All the acetylation sites involve evolutionarily conserved residues: 3 within the HMG-14/-17 nucleosomal binding domain and 4 in or near the bipartite nuclear localization domains of the proteins. In tissue culture cells the acetylation pattern is indicative of a selective process in which a subfraction of HMG-14 is preferentially acetylated. We find that the nucleosomal binding domain is a major target for acetylation in vivo and that the specific acetylation of HMG-14 by p300 weakens its interaction with nucleosome cores. Our results suggest that p300 modulates the interaction of HMG-14 with nucleosomes. Thus, p300 may affect chromatin-related activities not only by modifying histones or transcription factors but also by targeting structural nonhistone proteins.