Figure 3.

Model for how introduction of reversible H2B ubiquitylation may maintain a dynamic chromatin state. Chromatin in which H2B is not undergoing ubiquitylation and deubiquitylation may exist in a relatively static state (top panel), which is not amenable to the passage of transcriptional or replication machinery. A change in cellular conditions (metabolic state, extracellular signaling, detection of DNA damage, etc.) may induce the ubiquitylation of H2B at a given gene or replication origin. Such ubiquitylation is dynamic, and may be self-sustaining when coupled with ongoing transcription or DNA replication. Dynamic ubiquitylation is predicted to result in a fluctuating chromatin environment (lower panel; chromatin breathing), necessary for transcription/DNA replication. Ubiquitylation of H2B may enable the recruitment/retention of transcriptional/replication machinery (green ovals) at chromatin [possibly mediated by unknown protein(s) X (orange circles)], while deubiquitylation is required to enable the machinery to detach and advance along the DNA template. Blocking transcriptional elongation results in the loss of H2Bub from active genes, suggesting that transcription itself maintains the dynamic state of H2B ubiquitylation. Furthermore, replication stress results in the gradual loss of global H2Bub, and it is thus possible that DNA replication also maintains dynamic H2Bub.^8,9,28 Cessation of these processes may thus result in the underlying chromatin returning to a static and silent state (top panel).