Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin.,Nature Communications

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Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin.
Nature Communications ( IF 14.7 ) Pub Date : 2017-08-18 , DOI: 10.1038/s41467-017-00338-5
Aleix Bayona-Feliu _{1,

2,

3} , Anna Casas-Lamesa _{1,

2} , Oscar Reina ₂ , Jordi Bernués _{1,

2} , Fernando Azorín _{1,

2}

Affiliation

Linker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show that Drosophila histone H1 (dH1) prevents genome instability as indicated by the increased γH2Av (H2AvS137P) content and the high incidence of DNA breaks and sister-chromatid exchanges observed in dH1-depleted cells. Increased γH2Av occurs preferentially at heterochromatic elements, which are upregulated upon dH1 depletion, and is due to the abnormal accumulation of DNA:RNA hybrids (R-loops). R-loops accumulation is readily detectable in G1-phase, whereas γH2Av increases mainly during DNA replication. These defects induce JNK-mediated apoptosis and are specific of dH1 depletion since they are not observed when heterochromatin silencing is relieved by HP1a depletion. Altogether, our results suggest that histone H1 prevents R-loops-induced DNA damage in heterochromatin and unveil its essential contribution to maintenance of genome stability.While structural importance of linker histone H1 in packaging eukaryotic genome into chromatin is well known, its biological function remains poorly understood. Here the authors reveal that Drosophila linker histone H1 prevents DNA:RNA hybrids accumulation and genome instability in heterochromatin.

中文翻译：

连接组蛋白 H1 可防止异染色质中 R 环积累和基因组不稳定。

连接组蛋白 H1 是染色质的重要结构成分，可稳定核小体并将核丝压缩成更高级的结构。然而，组蛋白 H1 的生物学特性仍然知之甚少。在这里，我们发现果蝇组蛋白 H1 (dH1) 可以防止基因组不稳定，如在 dH1 耗尽的细胞中观察到的 γH2Av (H2AvS137P) 含量增加以及 DNA 断裂和姐妹染色单体交换发生率高所表明的那样。 γH2Av 增加优先发生在异染色质元件处，异染色质元件在 dH1 耗尽时上调，这是由于 DNA:RNA 杂合体（R 环）的异常积累所致。 R 环积累在 G1 期很容易检测到，而 γH2Av 主要在 DNA 复制期间增加。这些缺陷会诱导 JNK 介导的细胞凋亡，并且是 dH1 耗竭所特有的，因为当 HP1a 耗竭缓解异染色质沉默时，不会观察到这些缺陷。总而言之，我们的结果表明组蛋白 H1 可以防止异染色质中 R 环诱导的 DNA 损伤，并揭示其对维持基因组稳定性的重要贡献。虽然接头组蛋白 H1 在将真核基因组包装到染色质中的结构重要性是众所周知的，但其生物学功能仍然存在不太了解。在这里，作者揭示了果蝇接头组蛋白 H1 可以防止异染色质中 DNA:RNA 杂交体的积累和基因组不稳定。

更新日期：2017-08-17

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