TY - JOUR
T1 - Histone H3 Serine 28 Is Essential for Efficient Polycomb-Mediated Gene Repression in Drosophila
AU - Yung, Philip Yuk Kwong
AU - Stuetzer, Alexandra
AU - Fischle, Wolfgang
AU - Martinez, Anne Marie
AU - Cavalli, Giacomo
N1 - Funding Information:
We are grateful to Natalia Azpiazu, Konrad Basler, Walter Gehring, David Glover, Peter J. Harte, Alf Herzig, Martina Hödl, Ginés Morata, Jürg Müller, Nicolas Thomä, and Feng Tie for providing research reagents. Boyan Bonev, Thierry Cheutin, Satish Sati, and Bernd Schuettengruber provided helpful comments on the manuscript. We thank Chantal Cazevieille for assistance with scanning electron microscopy and in the use of the Montpellier RIO imaging facility. Research in the laboratory of G.C. was supported by grants from the European Research Council (ERC-2008-AdG no. 232947), the CNRS, the European Network of Excellence EpiGeneSys, the Agence Nationale de la Recherche, and the Fondation ARC pour la Recherche sur le Cancer. Funding of P.Y.K.Y. was supported by the Croucher Foundation and La Ligue contre le Cancer. Research in the laboratory of W.F. was supported by the Max Planck Society.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/6/9
Y1 - 2015/6/9
N2 - Trimethylation at histone H3K27 is central to the polycomb repression system. Juxtaposed to H3K27 is a widely conserved phosphorylatable serine residue (H3S28) whose function is unclear. To assess the importance of H3S28, we generated a Drosophila H3 histone mutant with a serine-to-alanine mutation at position 28. H3S28A mutant cells lack H3S28ph on mitotic chromosomes but support normal mitosis. Strikingly, all methylation states of H3K27 drop in H3S28A cells, leading to Hox gene derepression and to homeotic transformations in adult tissues. These defects are not caused by active H3K27 demethylation nor by the loss of H3S28ph. Biochemical assays show that H3S28A nucleosomes are a suboptimal substrate for PRC2, suggesting that the unphosphorylated state of serine 28 is important for assisting in the function of polycomb complexes. Collectively, our data indicate that the conserved H3S28 residue in metazoans has a role in supporting PRC2 catalysis.
AB - Trimethylation at histone H3K27 is central to the polycomb repression system. Juxtaposed to H3K27 is a widely conserved phosphorylatable serine residue (H3S28) whose function is unclear. To assess the importance of H3S28, we generated a Drosophila H3 histone mutant with a serine-to-alanine mutation at position 28. H3S28A mutant cells lack H3S28ph on mitotic chromosomes but support normal mitosis. Strikingly, all methylation states of H3K27 drop in H3S28A cells, leading to Hox gene derepression and to homeotic transformations in adult tissues. These defects are not caused by active H3K27 demethylation nor by the loss of H3S28ph. Biochemical assays show that H3S28A nucleosomes are a suboptimal substrate for PRC2, suggesting that the unphosphorylated state of serine 28 is important for assisting in the function of polycomb complexes. Collectively, our data indicate that the conserved H3S28 residue in metazoans has a role in supporting PRC2 catalysis.
UR - http://www.scopus.com/inward/record.url?scp=84930762366&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.04.055
DO - 10.1016/j.celrep.2015.04.055
M3 - Article
C2 - 26004180
AN - SCOPUS:84930762366
SN - 2211-1247
VL - 11
SP - 1437
EP - 1445
JO - Cell reports
JF - Cell reports
IS - 9
ER -