Figure 5.

Transcription-coupled stabilization of Bre1 fine-tunes H2B ubiquitylation. We found that the Rtf1 subunit of the PAF complex is important for stabilizing Bre1 and promoting H2BK123ub1. Given the close association of the PAF complex with transcribing RNAPII, we propose that Rtf1, residues 16–20 of histone H2A, and perhaps other proteins associated with the transcriptional apparatus interact with and stabilize Bre1 (indicated by solid black outline) to promote H2BK123ub1 in active regions of the genome. Once transcription is complete or in repressed regions, the absence of the transcriptional machinery leads to Bre1 instability (indicated by dashed outline). Transient interactions of Bre1/Rad6 with chromatin in repressed regions catalyze short-lived H2BK123ub1 (dashed outline) that is rapidly removed by the deubiquitylating enzymes Ubp8/10.