Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis.
Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis.
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DOI：
10.1186/s13072-016-0051-y
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发表时间：
2016
影响因子：
3.9
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Urahama T;Harada A;Maehara K;Horikoshi N;Sato K;Sato Y;Shiraishi K;Sugino N;Osakabe A;Tachiwana H;Kagawa W;Kimura H;Ohkawa Y;Kurumizaka H
人类组蛋白H3.5是由H3.3进化而来的非等位基因H3变异体。H3.5基因在人睾丸中高表达。然而，H3.5的功能仍然知之甚少。我们发现H3.5核小体不如H3.3核小体稳定。H3.5核小体的晶体结构表明，H3.5特异的Leu103残基对应于H3.3 Phe104残基，减少了与组蛋白H4的疏水相互作用。突变分析表明，H3.5特异的Leu103残基是H3.5核小体在体外和活细胞中不稳定的原因。H3.5蛋白存在于人的生精小管中，但在成熟精子中几乎没有发现。染色质免疫沉淀结合测序分析表明，H3.5在睾丸细胞的转录起始点(TSS)附近积累。我们对H3.5进行了全面的研究，发现H3.5核小体不稳定，H3.5蛋白在人睾丸TSS周围积聚。在精子发生过程中，不稳定的H3.5核小体可能参与TSSs周围的染色质动力学。
Human histone H3.5 is a non-allelic H3 variant evolutionally derived from H3.3. The H3.5 mRNA is highly expressed in human testis. However, the function of H3.5 has remained poorly understood. We found that the H3.5 nucleosome is less stable than the H3.3 nucleosome. The crystal structure of the H3.5 nucleosome showed that the H3.5-specific Leu103 residue, which corresponds to the H3.3 Phe104 residue, reduces the hydrophobic interaction with histone H4. Mutational analyses revealed that the H3.5-specific Leu103 residue is responsible for the instability of the H3.5 nucleosome, both in vitro and in living cells. The H3.5 protein was present in human seminiferous tubules, but little to none was found in mature sperm. A chromatin immunoprecipitation coupled with sequencing analysis revealed that H3.5 accumulated around transcription start sites (TSSs) in testicular cells. We performed comprehensive studies of H3.5, and found the instability of the H3.5 nucleosome and the accumulation of H3.5 protein around TSSs in human testis. The unstable H3.5 nucleosome may function in the chromatin dynamics around the TSSs, during spermatogenesis.