The aim of the research is to understand how the information encoded on the DNA specifies temporal, spatial, and quantitative patterns of control in the expression of eukaryotic genes. We propose two different strategies to approach this problem. The first one involves the use of """"""""reverse genetics"""""""" to identify transcriptional regulatory sequences involved in the control of the expression of the Drosophila hsp28 gene, both by heat shock and by ecdysone. We will use P element-mediated transformation of Drosophila embryos to analyze the effect of in vitro-constructed external deletions, linker-scanning mutants and point mutations on the transcription of hsp28 and its developmental and tissue-specific patterns of expression. These effects on transcription will be correlated with specific chromatin changes in the regions adjacent to the gene. The second approach involves the molecular analysis of the DNA lesions that cause mutant phenotypes at the forked and yellow loci of Drosophila. DNA sequences defining these genes will be cloned from specific mutant alleles which have a particularly interesting phenotype affecting the levels or tissue-specific expression of the RNAs encoded by these loci. From the correlation between the molecular lesion and the particular phenotype, we will be able to assign functional roles to different DNA sequences involved in control of transcription.

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National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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Johns Hopkins University
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Geyer, P K; Green, M M; Corces, V G (1990) Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. EMBO J 9:2247-56
Geyer, P K; Green, M M; Corces, V G (1988) Reversion of a gypsy-induced mutation at the yellow (y) locus of Drosophila melanogaster is associated with the insertion of a newly defined transposable element. Proc Natl Acad Sci U S A 85:3938-42
Geyer, P K; Richardson, K L; Corces, V G et al. (1988) Genetic instability in Drosophila melanogaster: P-element mutagenesis by gene conversion. Proc Natl Acad Sci U S A 85:6455-9
Geyer, P K; Green, M M; Corces, V G (1988) Mutant gene phenotypes mediated by a Drosophila melanogaster retrotransposon require sequences homologous to mammalian enhancers. Proc Natl Acad Sci U S A 85:8593-7
Hoffman, E P; Gerring, S L; Corces, V G (1987) The ovarian, ecdysterone, and heat-shock-responsive promoters of the Drosophila melanogaster hsp27 gene react very differently to perturbations of DNA sequence. Mol Cell Biol 7:973-81
Geyer, P K; Corces, V G (1987) Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes Dev 1:996-1004
Parkhurst, S M; Corces, V G (1987) Developmental expression of Drosophila melanogaster retrovirus-like transposable elements. EMBO J 6:419-24
Marlor, R L; Parkhurst, S M; Corces, V G (1986) The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins. Mol Cell Biol 6:1129-34
Parkhurst, S M; Corces, V G (1986) Mutations at the suppressor of forked locus increase the accumulation of gypsy-encoded transcripts in Drosophila melanogaster. Mol Cell Biol 6:2271-4
Parkhurst, S M; Corces, V G (1986) Interactions among the gypsy transposable element and the yellow and the suppressor of hairy-wing loci in Drosophila melanogaster. Mol Cell Biol 6:47-53

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