title: Mutations in CG8878, a novel putative protein kinase, enhance P element dependent silencing (PDS) and position effect variegation (PEV) in Drosophila melanogaster.
abstract: Genes in multicellular organisms are expressed as part of a developmental program that is largely dependent on self-perpetuating higher-order chromatin states. The mechanism of establishing and maintaining these epigenetic events is well studied in Drosophila. The first known example of an epigenetic effect was that of (PEV) in Drosophila, which has been shown to be due to gene silencing via heterochromatin formation. We are investigating a process similar to Position Effect Variegation (PEV) using a mini-w transgene, called Pci, inserted in the upstream regulatory region of ci. The mini-white+ transgene in Pci is expressed throughout the adult eye; however, when other P or KP elements are present, a variegated eye phenotype results indicating random w+ silencing during development. This P element dependent silencing (PDS) can be modified by the haplo-suppressors/triplo-enhancers, Su(var)205 and Su(var)3-7, indicating that these heterochromatic modifiers also act dose dependently in PDS. Here we use a spontaneous derivative mutation of Pci called PciE1 (E1) that variegates like PDS in the absence of P elements, presumably due to an adjacent gypsy element insertion, to screen for second-site modifier mutations that enhance variable silencing of white+ in E1. We isolated 7 mutations in CG8878, an essential gene, that enhance the E1 variegated phenotype. CG8878, a previously uncharacterized gene, potentially encodes a serine/threonine kinase whose closest Drosophila paralogue, ballchen (nhk-1), phosphorylates histones. These mutant alleles enhance both PDS at E1 and Position Effect Variegation (PEV) at w(m4), indicating a previously unknown common silencing mechanism between the two.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Allen
authors.initials: A
authors.lastname: McCracken
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Locke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000090266:Chromobox Protein Homolog 5; D055012:Chromosomal Position Effects / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D020868:Gene Silencing; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; C000716867:Su(var)205 protein, Drosophila; D000090266:Chromobox Protein Homolog 5; D011494:Protein Kinases; C000598275:CG8878 protein, Drosophila; D017346:Protein Serine-Threonine Kinases