H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin assembly

• Published in: EMBO reports 2019-10, Vol.20 (10), p.e48111-n/a
• Main Authors: Oya, Eriko, Nakagawa, Reiko, Yoshimura, Yuriko, Tanaka, Mayo, Nishibuchi, Gohei, Machida, Shinichi, Shirai, Atsuko, Ekwall, Karl, Kurumizaka, Hitoshi, Tagami, Hideaki, Nakayama, Jun‐ichi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Assembly; Chromatin; EMBO09; Enrichment; epigenetic gene silencing; Fission; fission yeast; Heterochromatin; Heterochromatin - metabolism; Histone H3; histone methylation; histone ubiquitylation; Histones; Histones - chemistry; Histones - metabolism; Immunoprecipitation; Lysine; Lysine - metabolism; Medicin och hälsovetenskap; Methylation; Methyltransferase; Methyltransferases - metabolism; Mutation; Mutation - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - metabolism; Spectrometry; Ubiquitin; Ubiquitin-protein ligase; Ubiquitination; Yeast; Yeasts
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.201948111

The methylation of histone H3 at lysine 9 (H3K9me), performed by the methyltransferase Clr4/SUV39H, is a key event in heterochromatin assembly. In fission yeast, Clr4, together with the ubiquitin E3 ligase Cul4, forms the Clr4 methyltransferase complex (CLRC), whose physiological targets and biological role are currently unclear. Here, we show that CLRC‐dependent H3 ubiquitylation regulates Clr4's methyltransferase activity. Affinity‐purified CLRC ubiquitylates histone H3, and mass spectrometric and mutation analyses reveal that H3 lysine 14 (H3K14) is the preferred target of the complex. Chromatin immunoprecipitation analysis shows that H3K14 ubiquitylation (H3K14ub) is closely associated with H3K9me‐enriched chromatin. Notably, the CLRC‐mediated H3 ubiquitylation promotes H3K9me by Clr4, suggesting that H3 ubiquitylation is intimately linked to the establishment and/or maintenance of H3K9me. These findings demonstrate a cross‐talk mechanism between histone ubiquitylation and methylation that is involved in heterochromatin assembly. Synopsis The Clr4 methyltransferase complex in fission yeast preferentially ubiquitylates H3K14. H3K14ub is linked to H3K9me‐enriched heterochromatin and promotes Clr4 methyltransferase activity. The Clr4 methyltransferase complex (CLRC) preferentially ubiquitylates H3K14. K14‐ubiquitylated histone H3 is enriched in heterochromatin. CLRC‐mediated H3 ubiquitylation promotes Clr4 methyltransferase activity. Graphical Abstract The Clr4 methyltransferase complex in fission yeast preferentially ubiquitylates H3K14. H3K14ub is linked to H3K9me‐enriched heterochromatin and promotes Clr4 methyltransferase activity.