Splitting the task: Ubp8 and Ubp10 deubiquitinate different cellular pools of H2BK123

Julia M. Schulze; Thomas Hentrich; Shima Nakanishi; Arvind Gupta; Eldon Emberly; Ali Shilatifard; Michael S. Kobor

doi:10.1101/gad.177220.111

Splitting the task: Ubp8 and Ubp10 deubiquitinate different cellular pools of H2BK123

¹Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada;
²Department of Medical Genetics,
³Department of Computing Science, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada;
⁴Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
⁵Department of Physics, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada

↵6 These authors contributed equally to this work.
↵7 These authors contributed equally to this work.

Abstract

Monoubiquitination of H2BK123 (H2BK123ub), catalyzed by Rad6/Bre1, is a transient histone modification with roles in transcription and is essential for establishing H3K4 and H3K79 trimethylations (H3K4me3 and H3K79me3). Here, we investigated the chromatin network around H2BK123ub by examining its localization and co-occurrence with its dependent marks as well as the transcription elongation mark H3K36me3 across the genome of Saccharomyces cerevisiae. In yeast, H2BK123ub is removed by the deubiquitinases Ubp8 and Ubp10, but their genomic target regions remain to be determined. Genome-wide maps of H2BK123ub in the absence of Ubp8 and Ubp10 revealed their distinct target loci, which were genomic sites enriched for H3K4me3 and H3K79me3, respectively. We propose an extended model of the H2BK123ub cross-talk by integrating existing relationships with the substrate specificities of Ubp8 and Ubp10 reported here.