title: The maternally expressed Drosophila gene encoding the chromatin-binding protein BJ1 is a homolog of the vertebrate gene Regulator of Chromatin Condensation, RCC1.
abstract: Using monoclonal antibodies I have identified a nuclear protein of Drosophila, BJ1 (Mr approximately 68 kd), and isolated its gene. Biochemical analysis demonstrates that the BJ1 protein is associated with nucleosomes and is released from chromatin by agents which intercalate into DNA, as previously shown for the high mobility group proteins (HMGs). On polytene chromosomes the protein is localized in all bands, with no preference for particular loci. Both the BJ1 protein and in particular the BJ1 mRNA are strongly expressed maternally. In early embryos all nuclei contain equal amounts of BJ1. During neuroblast formation, BJ1 mRNA becomes restricted to cells of the central nervous system, and higher protein levels are found in the nuclei of this tissue. In late embryonic stages, the mRNA almost completely disappears, but significant amounts of BJ1 protein persist until morphogenesis. The BJ1 gene encodes a 547 amino acid polypeptide featuring two different types of internal repeats. The sequence from amino acids 46 to 417 containing seven repeats of the first type has been highly conserved in evolution. 45% of the amino acids in this region are conserved in seven similar tandem repeats of the human gene Regulator of Chromatin Condensation, RCC1. The phenotype of a cell line carrying a mutation of RCC1 suggested a main function for this gene in cell cycle control. A yeast gene, SRM1/PRP20, also contains these repeats and shows 30% amino acid identity to BJ1 in this region. Mutations in this gene perturb mRNA metabolism, disrupt nuclear structure and alter the signal transduction pathway for the mating pheromone. Complementation experiments argue for a common function of these genes in the different species. I propose that their gene products bind to the chromatin to establish or maintain a proper higher order structure as a prerequisite for a regulated gene expression. Disruption of this structure could cause both mis-expression and default repression of genes, which might explain the pleiotropic phenotypes of the mutants.
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Frasch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001756:Blastoderm / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry* / Q000276:immunology; D002875:Chromosomes / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors; D007301:Insect Hormones / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D009866:Oogenesis / Q000235:genetics; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; D007301:Insect Hormones; D009687:Nuclear Proteins; D012333:RNA, Messenger; C068687:RCC1 protein, Drosophila; D004247:DNA