Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, People's Republic of China.
Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China; Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, Anhui 230026, People's Republic of China.
Structure. 2016 Oct 4;24(10):1810-1820. doi: 10.1016/j.str.2016.08.001. Epub 2016 Sep 8.
Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly.
组蛋白伴侣对于指导组蛋白的特定转录后修饰、保障核小体（组装/解组装）的组蛋白沉积（或解离）以及调节染色质结构以改变基因活性至关重要。已有报道称，HAT1 相互作用因子 1（Hif1）是一种 H3-H4 伴侣，参与端粒沉默和核小体（组装/解组装）。然而，Hif1 与组蛋白相互作用的结构基础仍然未知。在这里，我们报告了 Hif1 与 H2A-H2B 结合的复合物结构，以揭示 Hif1 对 H2A-H2B 二聚体和 H3-H4 四聚体结合的伴侣特异性。我们的发现表明，Hif1 通过不同的机制与 H2A-H2B 二聚体和 H3-H4 四聚体相互作用，这表明 Hif1 是 H2A-H2B 和 H3-H4 交替结合的关键支架。这些特异性是 Sim3-Hif1-NASP 中断四肽重复蛋白的保守特征，为研究它们在核小体（组装/解组装）中的潜在作用提供了线索。
