Journal article
Histone H3.3 phosphorylation promotes heterochromatin formation by inhibiting H3K9/K36 histone demethylase
M Udugama, B Vinod, FL Chan, L Hii, A Garvie, P Collas, P Kalitsis, D Steer, PP Das, P Tripathi, JR Mann, HPJ Voon, LH Wong
Nucleic Acids Research | Published : 2022
DOI: 10.1093/nar/gkac259
Abstract
Histone H3.3 is an H3 variant which differs from the canonical H3.1/2 at four residues, including a serine residue at position 31 which is evolutionarily conserved. The H3.3 S31 residue is phosphorylated (H3.3 S31Ph) at heterochromatin regions including telomeres and pericentric repeats. However, the role of H3.3 S31Ph in these regions remains unknown. In this study, we find that H3.3 S31Ph regulates heterochromatin accessibility at telomeres during replication through regulation of H3K9/K36 histone demethylase KDM4B. In mouse embryonic stem (ES) cells, substitution of S31 with an alanine residue (H3.3 A31 -phosphorylation null mutant) results in increased KDM4B activity that removes H3K9me3..
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Funding Acknowledgements
This work was supported by Worldwide Cancer Research, Brain Tumour Charity UK and NHMRC Australia. High-throughput sequencing was performed at the MHTP Medical Genomics Facility. This research was supported by use of the Nectar Research Cloud, a collaborative Australian research platform supported by the NCRIS-funded Australian Research Data Commons (ARDC).