Figure 2

Proposed models for the role of three H2A-DUBs - MYSM1, USP16 and USP3 - in regulating reversible modifications of histones. (a) Histone acetylation by PCAF (1) is proposed to promote removal of ubiquitin from lysine 119 (K119) in the H2A tail by associated MYSM1 (2). This promotes phosphorylation of H1 and its consequent dissociation from chromatin (3), facilitating transcriptional initiation and elongation of androgen receptor-regulated genes (4). (b) Deubiquitination of Ub-H2A by USP16 (1) leads to phosphorylation of H3 at serine 10 (S10) by the kinase Aurora B and subsequent G2/M cell-cycle progression (2). It also promotes transcriptional initiation of HOX gene transcription (3). (c) USP3 can remove ubiquitin from both H2A K119 and H2B K120 (1), promoting dephosphorylation of the H2AX variant histone and concomitant recovery from the ATM/ATR DNA-damage checkpoint during DNA repair (2). USP3 activity may also promote phosphorylation of H3 at S10, which is associated with entry into M phase (3). (a) adapted from Zhu et al. [12].