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Placing the HIRA Histone Chaperone Complex in the Chromatin Landscape

  • Nikolay A. Pchelintsev
  • , Tony McBryan
  • , Taranjit Singh Rai
  • , John VanTuyn
  • , Dominique Ray-Gallet
  • , Geneviève Almouzni
  • , Peter D. Adams

Research output: Contribution to journalArticlepeer-review

Abstract

The HIRA chaperone complex, comprised of HIRA, UBN1, and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand HIRA's function and mechanism, we integrated HIRA, UBN1, ASF1a, and histone H3.3 chromatin immunoprecipitation sequencing and gene expression analyses. Most HIRA-binding sites colocalize with UBN1, ASF1a, and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and coregulator composition at different classes of HIRA-bound regulatory sites. Underscoring this, we report physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodeling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites.

Original languageEnglish
Pages (from-to)1012-1019
Number of pages8
JournalCell Reports
Volume3
Issue number4
DOIs
Publication statusPublished (in print/issue) - 25 Apr 2013

Funding

We thank Pawel Herzyk, Julie Galbraith, and William Clark for DNA sequencing, David Strachan and Lynn McGarry for image analysis, and Sarah Kinkley, Adam Woolfe, David Vetrie, and Koorosh Koorfi for critical discussions. We thank members of the Adams laboratory and NIA program project members for critical discussions. Work in G.A.’s lab was supported by la Ligue Nationale contre le Cancer (Equipe labellisée Ligue). Work in the Adams laboratory was funded by CR-UK program project, C10652/A10250, and program project NIA AG031862-02.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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