title: HPC2 and ubinuclein define a novel family of histone chaperones conserved throughout eukaryotes.
abstract: While histone chaperones have been intensely studied, the roles of components of the Hir-Asf1 histone chaperone complex such as Hir3p and Hpc2p are poorly understood. Using sensitive protein sequence profile analyses we investigated the evolution of these proteins and showed that Hir3p and Hpc2p have a much wider phyletic pattern than was previously known. We established the animal histone-deacetylase-complex-interacting proteins, CAIN/CABIN, to be orthologs of Hir3p. They contain a conserved core of around 30 TPR-like bi-helical repeats that are likely to form a super-helical scaffold. We identified a conserved domain, the HUN domain, in all Hpc2p homologs, including animal ubinuclein/yemanuclein and the recently discovered vertebrate cell-cycle regulator FLJ25778. The HUN domain has a characteristic pattern of conserved acidic residues based on which we predict that it is a previously unrecognized histone-tail-binding chaperone. By analyzing various high-throughput data sets, such as RNAi knock-downs, genetic and protein interaction maps and cell-cycle-specific gene expression data, we present evidence that Hpc2p homologs might be deployed in specific processes of chromatin dynamics relating to cell-cycle progression in vertebrates and schizogony in Plasmodium. Beyond the conserved HUN domain these proteins show extensive divergence patterns in different eukaryotic lineages. Hence, we propose that Hpc2p homologs are probably involved in recruitment of the ancient conserved histone-loading Hir-Asf1 complex to different lineage-specific chromatin reorganization processes.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. sbalaji@mail.nih.gov
authors.forename: S
authors.initials: S
authors.lastname: Balaji
authors.forename: Lakshminarayan M
authors.initials: LM
authors.lastname: Iyer
authors.forename: L
authors.initials: L
authors.lastname: Aravind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D005057:Eukaryotic Cells / Q000378:metabolism*; D019143:Evolution, Molecular; D006657:Histones / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010802:Phylogeny; D010961:Plasmodium / Q000235:genetics; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D006657:Histones; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins