Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin

Aleix Bayona-Feliu, Anna Casas-Lamesa, Oscar Reina, Jordi Bernués () and Fernando Azorín ()
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Aleix Bayona-Feliu: Institute of Molecular Biology of Barcelona, IBMB, CSIC
Anna Casas-Lamesa: Institute of Molecular Biology of Barcelona, IBMB, CSIC
Oscar Reina: Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute of Science and Technology
Jordi Bernués: Institute of Molecular Biology of Barcelona, IBMB, CSIC
Fernando Azorín: Institute of Molecular Biology of Barcelona, IBMB, CSIC

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00338-5

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