title: Progressive methylation of ageing histones by Dot1 functions as a timer.
abstract: Post-translational modifications of histone proteins have a crucial role in regulating gene expression. If efficiently re-established after chromosome duplication, histone modifications could help propagate gene expression patterns in dividing cells by epigenetic mechanisms. We used an integrated approach to investigate the dynamics of the conserved methylation of histone H3 Lys 79 (H3K79) by Dot1. Our results show that methylation of H3K79 progressively changes after histone deposition, which is incompatible with a rapid copy mechanism. Instead, methylation accumulates on ageing histones, providing the cell with a timer mechanism to directly couple cell-cycle length to changes in chromatin modification on the nucleosome core.
authors.affiliation: Department of Molecular Cell Physiology, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: De Vos
authors.forename: Floor
authors.initials: F
authors.lastname: Frederiks
authors.forename: Marit
authors.initials: M
authors.lastname: Terweij
authors.forename: Tibor
authors.initials: T
authors.lastname: van Welsem
authors.forename: Kitty F
authors.initials: KF
authors.lastname: Verzijlbergen
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Iachina
authors.forename: Erik L
authors.initials: EL
authors.lastname: de Graaf
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.forename: Gideon
authors.initials: G
authors.lastname: Oudgenoeg
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bakker
authors.forename: Fred
authors.initials: F
authors.lastname: van Leeuwen
mesh_terms: D000375:Aging / Q000378:metabolism*; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase