Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Biology Faculty, Lomonosov Moscow State University, Moscow 119992, Russia.
Cells. 2022 Aug 10;11(16):2475. doi: 10.3390/cells11162475.
Histone N-terminal tails and their post-translational modifications affect various biological processes, often in a context-specific manner; the underlying mechanisms are poorly studied. Here, the role of individual N-terminal tails of histones H2A/H2B during transcription through chromatin was analyzed in vitro. spFRET data suggest that the tail of histone H2B (but not of histone H2A) affects nucleosome stability. Accordingly, deletion of the H2B tail (amino acids 1-31, but not 1-26) causes a partial relief of the nucleosomal barrier to transcribing RNA polymerase II (Pol II), likely facilitating uncoiling of DNA from the histone octamer during transcription. Taken together, the data suggest that residues 27-31 of histone H2B stabilize DNA-histone interactions at the DNA region localized ~25 bp in the nucleosome and thus interfere with Pol II progression through the region localized 11-15 bp in the nucleosome. This function of histone H2B requires the presence of the histone H2A N-tail that mediates formation of nucleosome-nucleosome dimers; however, nucleosome dimerization plays only a minimal role during transcription. Histone chaperone FACT facilitates transcription through all analyzed nucleosome variants, suggesting that H2A/H2B tails minimally interact with FACT during transcription; therefore, an alternative FACT-interacting domain(s) is likely involved in this process.
组蛋白 N 端尾部及其翻译后修饰影响各种生物过程,通常以特定于上下文的方式影响;其潜在机制研究甚少。在这里,分析了体外染色质转录过程中组蛋白 H2A/H2B 的各个 N 端尾部的作用。spFRET 数据表明,组蛋白 H2B 的尾部(而非组蛋白 H2A 的尾部)影响核小体稳定性。相应地,删除 H2B 尾部(氨基酸 1-31,但不是 1-26)会导致核小体对转录 RNA 聚合酶 II(Pol II)的障碍部分缓解,可能在转录过程中促进 DNA 从组蛋白八聚体解旋。总之,数据表明组蛋白 H2B 的残基 27-31 在 DNA 区域稳定 DNA-组蛋白相互作用,该区域在核小体中定位于~25 bp,从而干扰 Pol II 在核小体中定位于 11-15 bp 区域的进展。组蛋白 H2B 的此功能需要存在介导核小体二聚体形成的组蛋白 H2A N 端尾部;然而,核小体二聚体在转录过程中仅发挥最小作用。组蛋白伴侣 FACT 促进所有分析的核小体变体的转录,表明 H2A/H2B 尾部在转录过程中与 FACT 的相互作用最小;因此,可能涉及此过程的替代 FACT 相互作用结构域(多个)。