Document Type

Article

Publication Date

12-1-2011

Comments

This article has been peer reviewed. It was published in: PLoS Computational Biology.

Volume 7, Issue 12, December 2011, Article number e1002317.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240587/. DOI: 10.1371/journal.pcbi.1002317.

Copyright © 2011 Nguyen et al.

Abstract

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7.

PubMed ID

22194680

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