The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS.

To date, several classes of enzymes have been shown to affect transcription by catalyzing the modifications of nucleosomes via methylation. Employing our global proteomic screen, GPS, we have determined that the loss of Bur2, a component of the Bur1/Bur2 cyclin-dependent protein kinase, results in a decrease in histone H3(K4) methylation catalyzed by COMPASS. Furthermore, Bur1/Bur2 is required for histone H2B monoubiquitination by Rad6/Bre1. The effect on histone monoubiquitination and methylation is the result of defective Bur1/Bur2-mediated phosphorylation of Rad6 on its serine residue 120 and proper recruitment of the Paf1 complex to chromatin. We have also demonstrated that serine 120 of Rad6 is required for histone H2B monoubiquitination and the regulation of gene expression in vivo. Our results identify in vivo substrates for Bur1/Bur2, thus linking its role to transcriptional elongation and demonstrating a potential activation mechanism for histone H2B monoubiquitination by the Rad6/Bre1 complex.