title: Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo.
abstract: Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin-lysine linkage and ubiquitination cycles are not critical for trans-histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation.
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Vlaming
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Tibor
authors.initials: T
authors.lastname: van Welsem
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, The Netherlands Proteomics Centre Utrecht University, Utrecht, the Netherlands.
authors.forename: Erik L
authors.initials: EL
authors.lastname: de Graaf
authors.affiliation: Instituto de Biología Funcional y Genómica CSIC/University of Salamanca, Salamanca, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ontoso
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, The Netherlands Proteomics Centre Utrecht University, Utrecht, the Netherlands.
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.affiliation: Instituto de Biología Funcional y Genómica CSIC/University of Salamanca, Salamanca, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: San-Segundo
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, The Netherlands Proteomics Centre Utrecht University, Utrecht, the Netherlands.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands fred.v.leeuwen@nki.nl.
authors.forename: Fred
authors.initials: F
authors.lastname: van Leeuwen
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D054875:Ubiquitination / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D014452:Ubiquitins; D011495:Histone-Lysine N-Methyltransferase
keywords: Dot1; Set1; chromatin; crosstalk; histone ubiquitination