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Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo
Authors:Hanneke Vlaming  Tibor van Welsem  Erik L de Graaf  David Ontoso  AF Maarten Altelaar  Pedro A San-Segundo  Albert JR Heck  Fred van Leeuwen
Institution:1Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands;2Biomolecular Mass Spectrometry and Proteomics Group, The Netherlands Proteomics Centre, Utrecht University, Utrecht, the Netherlands;3Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, Salamanca, Spain
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.
Keywords:chromatin  crosstalk  Dot1  histone ubiquitination  Set1
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