Crystal structures of heterotypic nucleosomes containing histones H2A.Z and H2A.
Crystal structures of heterotypic nucleosomes containing histones H2A.Z and H2A.
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DOI：
10.1098/rsob.160127
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发表时间：
2016-06
期刊：
影响因子：
5.8
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Horikoshi N;Arimura Y;Taguchi H;Kurumizaka H
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。在转录调控过程中，形成含有 H2A.Z 和 H2A 各一个的异型 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 环区域将与异型核小体中规范 H2A 的相应区域发生空间冲突。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 L1环结构发生了巨大改变，而经典H2A L1环的结构没有发生任何变化，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核小体中起着重要作用。
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.