PP1?, PP1? and Wip-1 regulate H4S47 phosphorylation and deposition of histone H3 variant H3.3.

ABSTRACT: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1?, PP1? and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1?, PP1? and Wip1 bind H3-H4 in vitro and in vivo, whereas only PP1? and PP1?, but not Wip1, interact with Pak2 in vivo. These results suggest that PP1?, PP1? and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1? and PP1? also likely regulating the activity of Pak2. Finally, depletion of PP1?, PP1? and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC3783166 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature