Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.
Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2.
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DOI：
10.1107/s090744491302252x
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
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作者：
Horikoshi N;Sato K;Shimada K;Arimura Y;Osakabe A;Tachiwana H;Hayashi-Takanaka Y;Iwasaki W;Kagawa W;Harata M;Kimura H;Kurumizaka H
含有 H2A.Z.1 和 H2A.Z.2 的人核小体的晶体结构已确定。在核小体中 H2A.Z.1 和 H2A.Z.2 的 L1 环区域发现了结构多态性，这可能是由它们的柔性性质引起的。组蛋白 H2A.Z 变体在真核生物中广泛保守。已在脊椎动物中鉴定出两种同工型 H2A.Z.1 和 H2A.Z.2，它们可能在细胞生长和基因表达中具有不同的功能。然而，H2A.Z.1 和 H2A.Z.2 之间没有结构差异的报道。在本研究中，确定了含有人 H2A.Z.1 和 H2A.Z.2 的核小体的晶体结构。发现 H2A.Z.1 和 H2A.Z.2 的 L1 环区结构明显不同，尽管它们在该区域的氨基酸序列是相同的。这种结构多态性可能是由进化上发生在氨基酸 38 位置的取代以及 H2A.Z.1 和 H2A.Z.2 的 L1 环的柔性性质引起的。研究还发现，在活细胞中，H2A.Z.1 的核小体交换速度比 H2A.Z.2 更快。突变分析表明，第 38 位的氨基酸差异至少部分导致了 H2A.Z.1 和 H2A.Z.2 的独特动态。这些发现为理解细胞中H2A.Z.1和H2A.Z.2的调节和功能差异提供了重要的新信息。
The crystal structures of human nucleosomes containing H2A.Z.1 and H2A.Z.2 have been determined. Structural polymorphisms were found in the L1 loop regions of H2A.Z.1 and H2A.Z.2 in the nucleosomes that are likely to be caused by their flexible nature. The histone H2A.Z variant is widely conserved among eukaryotes. Two isoforms, H2A.Z.1 and H2A.Z.2, have been identified in vertebrates and may have distinct functions in cell growth and gene expression. However, no structural differences between H2A.Z.1 and H2A.Z.2 have been reported. In the present study, the crystal structures of nucleosomes containing human H2A.Z.1 and H2A.Z.2 were determined. The structures of the L1 loop regions were found to clearly differ between H2A.Z.1 and H2A.Z.2, although their amino-acid sequences in this region are identical. This structural polymorphism may have been induced by a substitution that evolutionally occurred at the position of amino acid 38 and by the flexible nature of the L1 loops of H2A.Z.1 and H2A.Z.2. It was also found that in living cells nucleosomal H2A.Z.1 exchanges more rapidly than H2A.Z.2. A mutational analysis revealed that the amino-acid difference at position 38 is at least partially responsible for the distinctive dynamics of H2A.Z.1 and H2A.Z.2. These findings provide important new information for understanding the differences in the regulation and functions of H2A.Z.1 and H2A.Z.2 in cells.