Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres.
The histone variant H3.3 is implicated in the formation and maintenance of specialized chromatin structure in metazoan cells. H3.3-containing nucleosomes are assembled in a replication-independent manner by means of dedicated chaperone proteins. We previously identified the death domain associated protein (Daxx) and the alpha-thalassemia X-linked mental retardation protein (ATRX) as H3.3-associated proteins. Here, we report that the highly conserved N terminus of Daxx interacts directly with variant-specific residues in the H3.3 core. Recombinant Daxx assembles H3.3/H4 tetramers on DNA templates, and the ATRX-Daxx complex catalyzes the deposition and remodeling of H3.3-containing nucleosomes. We find that the ATRX-Daxx complex is bound to telomeric chromatin, and that both components of this complex are required for H3.3 deposition at telomeres in murine embryonic stem cells (ESCs). These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex.
Lewis
Peter W
PW
Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
Elsaesser
Simon J
SJ
Noh
Kyung-Min
KM
Stadler
Sonja C
SC
Allis
C David
CD
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000378:metabolism*; D053595:Embryonic Stem Cells; D006570:Heterochromatin; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D016615:Telomere; D000075924:X-linked Nuclear Protein
D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D006570:Heterochromatin; D056488:Histone Chaperones; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009707:Nucleosomes; D004265:DNA Helicases; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein