Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, 739-8528, Japan.
Commun Biol. 2022 Aug 13;5(1):814. doi: 10.1038/s42003-022-03785-z.
Gene expression is regulated by the modification and accessibility of histone tails within nucleosomes. The histone chaperone FACT (facilitate chromatin transcription), comprising SPT16 and SSRP1, interacts with nucleosomes through partial replacement of DNA with the phosphorylated acidic intrinsically disordered (pAID) segment of SPT16; pAID induces an accessible conformation of the proximal histone H3 N-terminal tail (N-tail) in the unwrapped nucleosome with FACT. Here, we use NMR to probe the histone H2A and H2B tails in the unwrapped nucleosome. Consequently, both the H2A and H2B N-tails on the pAID-proximal side bind to pAID with robust interactions, which are important for nucleosome assembly with FACT. Furthermore, the conformations of these N-tails on the distal DNA-contact site are altered from those in the canonical nucleosome. Our findings highlight that FACT both proximally and distally regulates the conformations of the H2A and H2B N-tails in the asymmetrically unwrapped nucleosome.
基因表达受组蛋白尾部的修饰和可及性调节，这些尾部位于核小体中。组蛋白伴侣 FACT（促进染色质转录）由 SPT16 和 SSRP1 组成，通过用 SPT16 的磷酸化酸性无序（pAID）片段部分替代 DNA 与核小体相互作用；pAID 在 FACT 存在下诱导近端组蛋白 H3 N 末端尾巴（N 尾巴）的可及构象。在这里，我们使用 NMR 探测未包裹核小体中的组蛋白 H2A 和 H2B 尾巴。结果表明，pAID 近端的 H2A 和 H2B N 尾巴都与 pAID 具有强相互作用，这对于与 FACT 组装核小体很重要。此外，这些 N 尾巴在远端 DNA 接触位点的构象与经典核小体中的构象不同。我们的研究结果表明，FACT 从近端和远端调节不对称解开核小体中 H2A 和 H2B N 尾巴的构象。
