Biology Faculty, Lomonosov Moscow State University, Moscow, 119992, Russia.
Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Commun Biol. 2022 Jan 10;5(1):2. doi: 10.1038/s42003-021-02948-8.
FACT is a histone chaperone that participates in nucleosome removal and reassembly during transcription and replication. We used electron microscopy to study FACT, FACT:Nhp6 and FACT:Nhp6:nucleosome complexes, and found that all complexes adopt broad ranges of configurations, indicating high flexibility. We found unexpectedly that the DNA binding protein Nhp6 also binds to the C-terminal tails of FACT subunits, inducing more open geometries of FACT even in the absence of nucleosomes. Nhp6 therefore supports nucleosome unfolding by altering both the structure of FACT and the properties of nucleosomes. Complexes formed with FACT, Nhp6, and nucleosomes also produced a broad range of structures, revealing a large number of potential intermediates along a proposed unfolding pathway. The data suggest that Nhp6 has multiple roles before and during nucleosome unfolding by FACT, and that the process proceeds through a series of energetically similar intermediate structures, ultimately leading to an extensively unfolded form.
事实是一种组蛋白伴侣，参与转录和复制过程中的核小体去除和重组装。我们使用电子显微镜研究了 FACT、FACT：Nhp6 和 FACT：Nhp6：核小体复合物，发现所有复合物都采用广泛的构象范围，表明其具有高度的灵活性。我们出人意料地发现，DNA 结合蛋白 Nhp6 也与 FACT 亚基的 C 端尾部结合，即使在没有核小体的情况下，也会诱导 FACT 形成更开放的构象。因此，Nhp6 通过改变 FACT 的结构和核小体的性质来支持核小体的展开。与 FACT、Nhp6 和核小体形成的复合物也产生了广泛的结构，揭示了在提出的展开途径中存在大量潜在的中间产物。这些数据表明，Nhp6 在 FACT 展开核小体之前和期间具有多种作用，并且该过程通过一系列能量相似的中间结构进行，最终导致广泛展开的形式。
