DAXX envelops an H3.3-H4 dimer for H3.3-specific recognition

1] Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York 10065, USA [2] MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK [3].
Nature (Impact Factor: 42.35). 10/2012; 491. DOI: 10.1038/nature11608
Source: PubMed

ABSTRACT Histone chaperones represent a structurally and functionally diverse family of histone-binding proteins that prevent promiscuous interactions of histones before their assembly into chromatin. DAXX is a metazoan histone chaperone specific to the evolutionarily conserved histone variant H3.3. Here we report the crystal structures of the DAXX histone-binding domain with a histone H3.3-H4 dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidate the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended α-helical conformation to compete with major inter-histone, DNA and ASF1 interaction sites. Our structural studies identify recognition elements that read out H3.3-specific residues, and functional studies address the contributions of Gly 90 in H3.3 and Glu 225 in DAXX to chaperone-mediated H3.3 variant recognition specificity.

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    • "Through its association with (H3–H4) dimers (Elsasser et al. 2012) and disruption of (H3–H4) 2 tetramers in vitro (English et al. 2005; Natsume et al. 2007), ASF1A may facilitate the formation of (H3.3–H4) dimers that can be recruited by DAXX. This scenario is compatible with the H3.3 binding motifs for ASF1A and DAXX being distinct (English et al. 2005; Natsume et al. 2007) and with the exclusive association of (H3.3–H4) with ASF1 or DAXX recently explained by crystallography studies (Elsasser et al. 2012). ASF1A is not found in the same H3.3-containing "
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