HJURP Uses Distinct CENP-A Surfaces to Recognize and to Stabilize CENP-A/Histone H4 for Centromere Assembly

Emily A. Bassett, Jamie DeNizio, Meghan C. Barnhart-Dailey, Tanya Panchenko, Nikolina Sekulic, Danielle J. Rogers, Daniel R. Foltz, Ben E. Black*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Centromeres are defined by the presence of chromatin containing the histone H3 variant, CENP-A, whose assembly into nucleosomes requires the chromatin assembly factor HJURP. We find that whereas surface-exposed residues in the CENP-A targeting domain (CATD) are the primary sequence determinants for HJURP recognition, buried CATD residues that generate rigidity with H4 are also required for efficient incorporation into centromeres. HJURP contact points adjacent to the CATD on the CENP-A surface are not used for binding specificity but rather to transmit stability broadly throughout the histone fold domains of both CENP-A and H4. Furthermore, an intact CENP-A/CENP-A interface is a requirement for stable chromatin incorporation immediately upon HJURP-mediated assembly. These data offer insight into the mechanism by which HJURP discriminates CENP-A from bulk histone complexes and chaperones CENP-A/H4 for a substantial portion of the cell cycle prior to mediating chromatin assembly at the centromere. Using a combination of cell-based and biophysical approaches, Bassett et al. show that HJURP, the chromatin assembly factor for centromere-specifying histone H3 variant CENP-A, recognizes specific discontinuous surface residues on the histone. HJURP binding confers stability to CENP-A/histone H4 and, together with an intact CENP-A/CENP-A interface, allows for centromere assembly.

Original languageEnglish (US)
Pages (from-to)749-762
Number of pages14
JournalDevelopmental Cell
Volume22
Issue number4
DOIs
StatePublished - Apr 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'HJURP Uses Distinct CENP-A Surfaces to Recognize and to Stabilize CENP-A/Histone H4 for Centromere Assembly'. Together they form a unique fingerprint.

  • Cite this

    Bassett, E. A., DeNizio, J., Barnhart-Dailey, M. C., Panchenko, T., Sekulic, N., Rogers, D. J., Foltz, D. R., & Black, B. E. (2012). HJURP Uses Distinct CENP-A Surfaces to Recognize and to Stabilize CENP-A/Histone H4 for Centromere Assembly. Developmental Cell, 22(4), 749-762. https://doi.org/10.1016/j.devcel.2012.02.001