Abstract

The work proposed concerns two major areas of study: I. Analysis of the relationship between long range cis transcriptional regulatory effects and synapsis-dependent trans regulatory effects in Drosophila: Our analysis to date suggests that these two classes of effects result from the properties of the same regulatory elements - enhancers or enhancer-like elements. If this relationship proves to be general, it represents a fundamentally new insight into the intractable problems of how enhancers work and what transvection effects are. Lines of experimentation include (a) identifying cases of activation of heterologous promotors by the presumptive enhancer at the white locus of Drosophila under conditions that allow convenient test for a corresponding synapsis dependent trans effect and (b) defining the portions of a promoter whose expression apparently represses (in cis and in synapsed trans) white expression when the two are juxtaposed in the w-DZL allele. II. Analysis of supressor-of-white-apricot and suppressor-of-white-spotted, two genes that apparently code for diffusable, trans-acting transcription factors: These genes represesnt two of the best opportunities in metazoan biology to study trans-acting transcription factors. Both of these genes are amenable to sophisticated genetic manipulation and we have cloned and partially analyzed the transcription units at both loci. The su(w-sp) gene behaves as if it codes for a repressor of white transcription and lines of experimentation include characterization of the tissue- and subcellular localization of the protein product of this locus with the objective of defining its role in regulating white transcription. The su(w-a) gene appears to activate its own transcription and lines of experimentation include definitive tests of this hypothesis and analysis of the cis-acting elements at su(w-a) responsive to the presumptive positive autoregulatory signal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032003-05
Application #
3280519
Study Section
Genetics Study Section (GEN)
Project Start
1983-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Zachar, Z; Chou, T B; Kramer, J et al. (1994) Analysis of autoregulation at the level of pre-mRNA splicing of the suppressor-of-white-apricot gene in Drosophila. Genetics 137:139-50
Zachar, Z; Kramer, J; Bingham, P M (1994) Looking at mRNA splicing and transport in situ. Methods Cell Biol 44:599-611
Spikes, D A; Kramer, J; Bingham, P M et al. (1994) SWAP pre-mRNA splicing regulators are a novel, ancient protein family sharing a highly conserved sequence motif with the prp21 family of constitutive splicing proteins. Nucleic Acids Res 22:4510-9
Zachar, Z; Kramer, J; Mims, I P et al. (1993) Evidence for channeled diffusion of pre-mRNAs during nuclear RNA transport in metazoans. J Cell Biol 121:729-42
Spikes, D; Bingham, P M (1992) Analysis of spliceosome assembly and the structure of a regulated intron in Drosophila in vitro splicing extracts. Nucleic Acids Res 20:5719-27
Zachar, Z; Bingham, P M (1989) Suppressible insertion-induced mutations in Drosophila. Prog Nucleic Acid Res Mol Biol 36:87-98
Bingham, P M; Chou, T B; Mims, I et al. (1988) On/off regulation of gene expression at the level of splicing. Trends Genet 4:134-8
Zachar, Z; Chou, T B; Bingham, P M (1987) Evidence that a regulatory gene autoregulates splicing of its transcript. EMBO J 6:4105-11
Zachar, Z; Garza, D; Chou, T B et al. (1987) Molecular cloning and genetic analysis of the suppressor-of-white-apricot locus from Drosophila melanogaster. Mol Cell Biol 7:2498-505
Bingham, P M; Chapman, C H (1986) Evidence that white-blood is a novel type of temperature-sensitive mutation resulting from temperature-dependent effects of a transposon insertion on formation of white transcripts. EMBO J 5:3343-51

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