Structure and function of human histone H3.Y nucleosome.
Structure and function of human histone H3.Y nucleosome.
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DOI：
10.1093/nar/gkw202
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发表时间：
2016-07-27
影响因子：
14.9
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Kujirai T;Horikoshi N;Sato K;Maehara K;Machida S;Osakabe A;Kimura H;Ohkawa Y;Kurumizaka H
组蛋白H3.Y是灵长类动物特异性的、远缘的H3变体。它在进化上来源于H3.3，并且可能在转录调节中起作用。然而，H3.Y调节转录的机制尚未阐明。在本研究中，我们确定了H3.Y核小体的晶体结构，并发现许多H3.Y特异性残基位于核小体的进入/退出位点。生化分析显示，H3.Y核小体的DNA末端比H3.3核小体的DNA末端更灵活，尽管H3.Y核小体在体外和体内都很稳定。有趣的是，与H3.3核小体相比，压缩核小体DNA的接头组蛋白H1似乎与H3.Y核小体的结合效率较低。H3.Y核小体的这些特征在H3.Y/H3.3异型核小体中也是保守的，H3.Y/H3.3异型核小体可能是细胞中的主要形式。在人类细胞中，H3.Y优先聚集在转录起始位点（TSS）周围。总之，转录起始位点周围的含H3.Y的核小体可以形成松弛的染色质，允许转录因子进入，以调节特定基因的转录状态。
Histone H3.Y is a primate-specific, distant H3 variant. It is evolutionarily derived from H3.3, and may function in transcription regulation. However, the mechanism by which H3.Y regulates transcription has not been elucidated. In the present study, we determined the crystal structure of the H3.Y nucleosome, and found that many H3.Y-specific residues are located on the entry/exit sites of the nucleosome. Biochemical analyses revealed that the DNA ends of the H3.Y nucleosome were more flexible than those of the H3.3 nucleosome, although the H3.Y nucleosome was stable in vitro and in vivo. Interestingly, the linker histone H1, which compacts nucleosomal DNA, appears to bind to the H3.Y nucleosome less efficiently, as compared to the H3.3 nucleosome. These characteristics of the H3.Y nucleosome are also conserved in the H3.Y/H3.3 heterotypic nucleosome, which may be the predominant form in cells. In human cells, H3.Y preferentially accumulated around transcription start sites (TSSs). Taken together, H3.Y-containing nucleosomes around transcription start sites may form relaxed chromatin that allows transcription factor access, to regulate the transcription status of specific genes.