The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation

Pierre Bourguet, Colette L. Picard, Ramesh Yelagandula, Thierry Pélissier, Zdravko J. Lorković, Suhua Feng, Marie-Noëlle Pouch-Pélissier, Anna Schmücker, Steven E. Jacobsen, Frédéric Berger and Olivier Mathieu ()
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Pierre Bourguet: CNRS, Université Clermont Auvergne, Inserm, Institut Génétique Reproduction et Développement (iGReD)
Colette L. Picard: University of California at Los Angeles
Ramesh Yelagandula: Vienna BioCenter (VBC)
Thierry Pélissier: CNRS, Université Clermont Auvergne, Inserm, Institut Génétique Reproduction et Développement (iGReD)
Zdravko J. Lorković: Vienna BioCenter (VBC)
Suhua Feng: University of California at Los Angeles
Marie-Noëlle Pouch-Pélissier: CNRS, Université Clermont Auvergne, Inserm, Institut Génétique Reproduction et Développement (iGReD)
Anna Schmücker: Vienna BioCenter (VBC)
Steven E. Jacobsen: University of California at Los Angeles
Frédéric Berger: Vienna BioCenter (VBC)
Olivier Mathieu: CNRS, Université Clermont Auvergne, Inserm, Institut Génétique Reproduction et Développement (iGReD)

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract In flowering plants, heterochromatin is demarcated by the histone variant H2A.W, elevated levels of the linker histone H1, and specific epigenetic modifications, such as high levels of DNA methylation at both CG and non-CG sites. How H2A.W regulates heterochromatin organization and interacts with other heterochromatic features is unclear. Here, we create a h2a.w null mutant via CRISPR-Cas9, h2a.w-2, to analyze the in vivo function of H2A.W. We find that H2A.W antagonizes deposition of H1 at heterochromatin and that non-CG methylation and accessibility are moderately decreased in h2a.w-2 heterochromatin. Compared to H1 loss alone, combined loss of H1 and H2A.W greatly increases accessibility and facilitates non-CG DNA methylation in heterochromatin, suggesting co-regulation of heterochromatic features by H2A.W and H1. Our results suggest that H2A.W helps maintain optimal heterochromatin accessibility and DNA methylation by promoting chromatin compaction together with H1, while also inhibiting excessive H1 incorporation.

Date: 2021
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DOI: 10.1038/s41467-021-22993-5

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