Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex

Daniel Ricketts, M., Frederick, B., Hoff, H., Tang, Y., Schultz, D. C., Rai, T., Grazia, M., Adams, P. and Marmorstein, R. (2015) Ubinuclein-1 confers histone H3.3-specific-binding by the HIRA histone chaperone complex. Nature Communications, 6, 7711. (doi: 10.1038/ncomms8711) (PMID:26159857) (PMCID:PMC4510971)

[img]
Preview
Text
109536.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

Abstract

Histone chaperones bind specific histones to mediate their storage, eviction or deposition from/or into chromatin. The HIRA histone chaperone complex, composed of HIRA, ubinuclein-1 (UBN1) and CABIN1, cooperates with the histone chaperone ASF1a to mediate H3.3-specific binding and chromatin deposition. Here we demonstrate that the conserved UBN1 Hpc2-related domain (HRD) is a novel H3.3-specific-binding domain. Biochemical and biophysical studies show the UBN1-HRD preferentially binds H3.3/H4 over H3.1/H4. X-ray crystallographic and mutational studies reveal that conserved residues within the UBN1-HRD and H3.3 G90 as key determinants of UBN1–H3.3-binding specificity. Comparison of the structure with the unrelated H3.3-specific chaperone DAXX reveals nearly identical points of contact between the chaperone and histone in the proximity of H3.3 G90, although the mechanism for H3.3 G90 recognition appears to be distinct. This study points to UBN1 as the determinant of H3.3-specific binding and deposition by the HIRA complex.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Adams, Professor Peter and Rai, Dr Taranjit
Authors: Daniel Ricketts, M., Frederick, B., Hoff, H., Tang, Y., Schultz, D. C., Rai, T., Grazia, M., Adams, P., and Marmorstein, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Nature Communications 6:7711
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record