Chromatin Signaling to Kinetochores: Transregulation of Dam1 Methylation by Histone H2B Ubiquitination

SummaryHistone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory crosstalk intrans between a histone modification and modification on a nonhistone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries.

Graphical AbstractFigure optionsDownload high-quality image (173 K)Download as PowerPoint slideHighlights
► Methylation of the kinetochore protein Dam1 is regulated by transcription factors
► Prior H2BK123 ubiquitination is required for Dam1 methylation by Set1
► Histone modification states can regulate non-DNA-templated processes