This investigation is a case study of how a higher organism controls a simple development expression pattern. The genes to be studied are the pair of closely spaced and divergently transcribed yolk protein genes of Drosophila melanogaster. These genes have an expression pattern that is highly differentiated with respect to development of the organism and, though fairly simple, has several specificities: tissue, sex, timing within the lifetime of a cell, and hormonal response. The first objective of the project is to identify components of the mechanism by a combination of: 1) experiments which use in vitro mutagenesis and germ line transformation to identify sequences that are necessary and/or sufficient for aspects of the normal expression pattern; and 2) experiments which use DNA binding assays and cell free- transcription to identify and characterize proteins and DNA sequences which influence the yp expression pattern. The second objective is to examine interactions between identified DNA components. This will be done by manipulating component number, arrangement, and kind and then testing the consequences by germ line transformation, cell free transcription, and physical studies of protein-DNA interactions. The third objective is to determine the developmental specificities of cis-acting DNA elements which control a gene that acts in trans to determine one aspect of the yp1-2 transcription pattern.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021626-15
Application #
3270608
Study Section
Genetics Study Section (GEN)
Project Start
1977-12-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
15
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Jacoby, D B; Wensink, P C (1996) DNA binding specificities of YPF1, a Drosophila homolog to the DNA binding subunit of human DNA-dependent protein kinase, Ku. J Biol Chem 271:16827-32
An, W; Wensink, P C (1995) Integrating sex- and tissue-specific regulation within a single Drosophila enhancer. Genes Dev 9:256-66
An, W; Wensink, P C (1995) Three protein binding sites form an enhancer that regulates sex- and fat body-specific transcription of Drosophila yolk protein genes. EMBO J 14:1221-30
Lossky, M; Wensink, P C (1995) Regulation of Drosophila yolk protein genes by an ovary-specific GATA factor. Mol Cell Biol 15:6943-52
O'Donnell, K H; Chen, C T; Wensink, P C (1994) Insulating DNA directs ubiquitous transcription of the Drosophila melanogaster alpha 1-tubulin gene. Mol Cell Biol 14:6398-408
Jacoby, D B; Wensink, P C (1994) Yolk protein factor 1 is a Drosophila homolog of Ku, the DNA-binding subunit of a DNA-dependent protein kinase from humans. J Biol Chem 269:11484-91
O'Donnell, K H; Wensink, P C (1994) GAGA factor and TBF1 bind DNA elements that direct ubiquitous transcription of the Drosophila alpha 1-tubulin gene. Nucleic Acids Res 22:4712-8
Coschigano, K T; Wensink, P C (1993) Sex-specific transcriptional regulation by the male and female doublesex proteins of Drosophila. Genes Dev 7:42-54
Logan, S K; Wensink, P C (1990) Ovarian follicle cell enhancers from the Drosophila yolk protein genes: different segments of one enhancer have different cell-type specificities that interact to give normal expression. Genes Dev 4:613-23
Logan, S K; Garabedian, M J; Wensink, P C (1989) DNA regions that regulate the ovarian transcriptional specificity of Drosophila yolk protein genes. Genes Dev 3:1453-61

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