DAXX-dependent supply of soluble (H3.3-H4) dimers into PML bodies pending deposition into chromatin
- ↵* Corresponding author; email: philippe.collas{at}medisin.uio.no
Abstract
Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multi-step targeting of newly synthesized epitope-tagged H3.3 to chromatin via PML bodies. H3.3 is recruited to PML bodies in a DAXX--dependent manner, a process facilitated by ASF1A. DAXX is required for enrichment of ATRX, but not ASF1A or HIRA, with PML. Nonetheless, the chaperones co-localize with H3.3 at PML bodies and are found in one or more complexes with PML. Both DAXX and PML are necessary to prevent accumulation of a soluble, non-incorporated, pool of H3.3. H3.3 targeting to PML is enhanced with an (H3.3-H4)2 tetramerization mutant of H3.3, suggesting H3.3 recruitment to PML as an (H3.3-H4) dimer rather than as a tetramer. Our data support a model of DAXX-mediated recruitment of (H3.3-H4) dimers to PML bodies, which may function as triage centers for H3.3 deposition into chromatin by distinct chaperones.
- Received May 3, 2012.
- Accepted November 30, 2012.
- © 2012, Published by Cold Spring Harbor Laboratory Press
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