title: DAXX-dependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin.
abstract: Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multistep 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 colocalize 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, nonincorporated 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.
authors.affiliation: Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
authors.forename: Erwan
authors.initials: E
authors.lastname: Delbarre
authors.forename: Kristina
authors.initials: K
authors.lastname: Ivanauskiene
authors.forename: Thomas
authors.initials: T
authors.lastname: Küntziger
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D006367:HeLa Cells; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000075924:X-linked Nuclear Protein
chemical_list: C491641:ASF1A protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C086057:HIRA protein, human; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D009707:Nucleosomes; D014157:Transcription Factors; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein