title: Genetic and molecular complexity of the position effect variegation modifier mod(mdg4) in Drosophila.
abstract: mod(mdg4), also known as E(var)3-93D, is involved in a variety of processes, such as gene silencing in position effect variegation (PEV), the control of gypsy insulator sequences, regulation of homeotic gene expression, and programmed cell death. We have isolated a large number of mod(mdg4) cDNAs, representing 21 different isoforms generated by alternative splicing. The deduced proteins are characterized by a common N terminus of 402 amino acids, including the BTB/POZ-domain. Most of the variable C termini contain a new consensus sequence, including four positioned hydrophobic amino acids and a Cys(2)His(2) motif. Using specific antibodies for two protein isoforms, we demonstrate different distributions of the corresponding proteins on polytene chromosomes. Mutations in the genomic region encoding exons 1-4 show enhancement of PEV and homeotic transformation and affect viability and fertility. Homeotic and PEV phenotypes are enhanced by mutations in other trx-group genes. A transgene containing the common 5' region of mod(mdg4) that is present in all splice variants known so far partially rescues the recessive lethality of mod(mdg4) mutant alleles. Our data provide evidence that the molecular and genetic complexity of mod(mdg4) is caused by a large set of individual protein isoforms with specific functions in regulating the chromatin structure of different sets of genes throughout development.
authors.affiliation: Institute of Genetics, Martin-Luther University of Halle, D-06108 Halle, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Büchner
authors.forename: P
authors.initials: P
authors.lastname: Roth
authors.forename: G
authors.initials: G
authors.lastname: Schotta
authors.forename: V
authors.initials: V
authors.lastname: Krauss
authors.forename: H
authors.initials: H
authors.lastname: Saumweber
authors.forename: G
authors.initials: G
authors.lastname: Reuter
authors.forename: R
authors.initials: R
authors.lastname: Dorn
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D016384:Consensus Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D007814:Larva; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009866:Oogenesis; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011679:Pupa; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014170:Transformation, Genetic
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C063460:Trl protein, Drosophila; C101384:mod(mdg4) protein, Drosophila