Tethering of HP1 proteins to chromatin is relieved by phosphoacetylation of histone H3.
Histone H3 lysine 9 methylation is associated with long-term transcriptional repression through recruitment of heterochromatin protein 1 (HP1) proteins. These proteins are believed to promote the formation of dense chromatin structures interfering with DNA accessibility. During the G2 phase of the cell cycle, HP1 proteins are delocalized from foci of pericentromeric heterochromatin, while a wave of H3 serine 10 phosphorylation is initiated within these regions. Here, we show that in vivo phosphorylation of serine 10 in G2 can occur on histone tails methylated on lysine 9. Unexpectedly, this modification favours rather than prevents HP1 binding to chromatin. Dissociation of HP1 from the methylated histone H3 tails is observed only after a third modification by acetylation of lysine 14, which occurs in prophase. We propose that phosphoacetylation of histone H3 could be a general mechanism allowing the cell to overcome HP1-mediated transcriptional repression.
Mateescu
Bogdan
B
Expression Génétique et Maladies, URA1644 du CNRS, Département de Biologie du Développement, Institut Pasteur, Bât. Fernbach, 25, Rue du Docteur Roux, 7S724, Paris Cedex 15, France.
England
Patrick
P
Halgand
Frederic
F
Yaniv
Moshe
M
Muchardt
Christian
C
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D016195:G2 Phase; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D046911:Macromolecular Substances; D008745:Methylation; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D020349:Surface Plasmon Resonance
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D046911:Macromolecular Substances; D010455:Peptides; D011993:Recombinant Fusion Proteins; D000090266:Chromobox Protein Homolog 5; D012694:Serine; D008239:Lysine