包含组蛋白H2A.Z和H2A的异型核小体的晶体结构
Crystal structures of heterotypic nucleosomes containing histones H2A.Z and H2A.
作者信息
Horikoshi Naoki, Arimura Yasuhiro, Taguchi Hiroyuki, Kurumizaka Hitoshi
机构信息
Research Institute for Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
出版信息
Open Biol. 2016 Jun;6(6). doi: 10.1098/rsob.160127.
H2A.Z is incorporated into nucleosomes located around transcription start sites and functions as an epigenetic regulator for the transcription of certain genes. During transcriptional regulation, the heterotypic H2A.Z/H2A nucleosome containing one each of H2A.Z and H2A is formed. However, previous homotypic H2A.Z nucleosome structures suggested that the L1 loop region of H2A.Z would sterically clash with the corresponding region of canonical H2A in the heterotypic nucleosome. To resolve this issue, we determined the crystal structures of heterotypic H2A.Z/H2A nucleosomes. In the H2A.Z/H2A nucleosome structure, the H2A.Z L1 loop structure was drastically altered without any structural changes of the canonical H2A L1 loop, thus avoiding the steric clash. Unexpectedly, the heterotypic H2A.Z/H2A nucleosome is more stable than the homotypic H2A.Z nucleosome. These data suggested that the flexible character of the H2A.Z L1 loop plays an essential role in forming the stable heterotypic H2A.Z/H2A nucleosome.
H2A.Z被整合到位于转录起始位点周围的核小体中，并作为某些基因转录的表观遗传调节因子发挥作用。在转录调控过程中，会形成同时包含一个H2A.Z和一个H2A的异型H2A.Z/H2A核小体。然而，先前的同型H2A.Z核小体结构表明，H2A.Z的L1环区域在空间上会与异型核小体中经典H2A的相应区域发生冲突。为了解决这个问题，我们确定了异型H2A.Z/H2A核小体的晶体结构。在H2A.Z/H2A核小体结构中，H2A.Z的L1环结构发生了显著改变，而经典H2A的L1环没有任何结构变化，从而避免了空间冲突。出乎意料的是，异型H2A.Z/H2A核小体比同型H2A.Z核小体更稳定。这些数据表明，H2A.Z L1环的柔性特征在形成稳定的异型H2A.Z/H2A核小体中起着至关重要的作用。
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