title: A Molecular Prospective for HIRA Complex Assembly and H3.3-Specific Histone Chaperone Function.
abstract: Incorporation of variant histone sequences, in addition to post-translational modification of histones, serves to modulate the chromatin environment. Different histone chaperone proteins mediate the storage and chromatin deposition of variant histones. Although the two non-centromeric histone H3 variants, H3.1 and H3.3, differ by only 5 aa, replacement of histone H3.1 with H3.3 can modulate the transcription for highly expressed and developmentally required genes, lead to the formation of repressive heterochromatin, or aid in DNA and chromatin repair. The human histone cell cycle regulator (HIRA) complex composed of HIRA, ubinuclein-1, CABIN1, and transiently anti-silencing function 1, forms one of the two complexes that bind and deposit H3.3/H4 into chromatin. A number of recent biochemical and structural studies have revealed important details underlying how these proteins assemble and function together as a multiprotein H3.3-specific histone chaperone complex. Here, we present a review of existing data and present a new model for the assembly of the HIRA complex and for the HIRA-mediated incorporation of H3.3/H4 into chromatin.
authors.affiliation: Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: M Daniel
authors.initials: MD
authors.lastname: Ricketts
authors.affiliation: Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Program, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: marmor@mail.med.upenn.edu.
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004260:DNA Repair; D005786:Gene Expression Regulation; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C491641:ASF1A protein, human; C491640:ASF1B protein, human; D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C086057:HIRA protein, human; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D014157:Transcription Factors; C406814:UBN1 protein, human
keywords: CABIN1; HIRA; UBN1; histone H3.3; histone chaperones