title: Placing the HIRA histone chaperone complex in the chromatin landscape.
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.
authors.affiliation: CR-UK Beatson Labs, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Pchelintsev
authors.forename: Tony
authors.initials: T
authors.lastname: McBryan
authors.forename: Taranjit Singh
authors.initials: TS
authors.lastname: Rai
authors.forename: John
authors.initials: J
authors.lastname: van Tuyn
authors.forename: Dominique
authors.initials: D
authors.lastname: Ray-Gallet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
authors.forename: Peter D
authors.initials: PD
authors.lastname: Adams
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D056426:Genetic Loci; D006367:HeLa Cells; D056488:Histone Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C491641:ASF1A protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C086057:HIRA protein, human; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C406814:UBN1 protein, human