On Nov. 11, 2012, Nature Structural & Molecular Biology (NSMB) published online a research article entitled “Structure of the variant histone H3.3–H4 heterodimer in complex with its chaperone DAXX”, which from the groups of Prof. Rui-Ming Xu and Prof. Guohong Li at the Institute of Biophysics, Chinese Academy of Sciences and their collaborator Prof. Zhiguo Zhang at Mayo Clinic, USA. (http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.2439.html)

Researches between histones, histone variants and histone chaperones are hotspots in epigenetics. Histone variants can replace canonical histones in some cases and play important role in regulating chromatin structure. H3.3 is a histone variant of H3.1 and its two deposition pathways are mediated by histone chaperones DAXX and HIRA. H3.3 differs from H3.1 by only five amino acids, but DAXX can distinguish the two with high precision and bind H3.3 specifically. The molecular basis for how DAXX specific recognition of H3.3 remains unknown.

In this study, researchers determined the structure of DAXX-H3.3-H4 complex at a 2.8Å resolution, and together with mutagenesis and cell-based targeting results, they revealed a mainly two-site recognition mechanism: the Ala87 of H3.3 is a small hydrophobic residue preferred by the shallow hydrophobic pocket formed by Cys338 and Leu340 in DAXX and DAXX preferen­tially selects the Gly90 of H3.3 over the hydrophobic residue Met90 of H3.1. An alanine at residue 87 or a glycine at residue 90 can independently direct the recognition by DAXX. The results provide insights into the specificity for H3.3 recognition, and the structural basis is important for delineating H3.3 deposition pathways.

This work was supported by grants from the Ministry of Science and Technology of China, the Natural Science Foundation of China and Chinese Academy of Sciences.

Figure legend: The crystal structure of the DAXX–H3.3–H4 complex.