DETERMINANTS OF GENE REGULATION

Project: Research project

Project Details

Description

The longterm goal of the proposed research is to determine how genetic
regulatory systems are determined by the joint contribution of their
developmental and evolutionary histories. The Drosophila glucose
dehydrogenase gene (Gld) will be used as a model system to study these
determinants of gene regulation because Gld's tissue-specific
regulation in the adult reproductive tract is highly variable among a
variety of species in the genus Drosophila. The research strategy will
be to use a combination of in vitro mutagenesis and gene transformation
to critically test hypotheses regarding the role of cis-elements and
trans-acting factors responsible for species' differences in
developmental expression of GLD. The specific aims are largely focused
on elucidating the regulatory factors underlying GLD expression in the
reproductive organs of both males and females, and, in parallel,
identifying regulatory differences between species. Since the sex-
determination genes tra and tra-2 are required for the unique tissue-
specific pattern of GLD expression in D. melanogaster, the Gld
regulatory elements that respond to them will be mapped. Misregulation
of tra and tra-2 in D. melanogaster leads to ectopic patterns of GLD
expression in the reproductive tract that mimic normal patterns seen
other Drosophila species. A hypothesis that other species' Gld genes
differ in their response to the sex-determination genes will be tested.
A newly devised genetic method for identifying genes that encode tissue
specific transcription factors will be used to isolate such genes that
regulate Gld.

Knowledge of gene function alone provides insufficient and sometimes
misleading information for understanding why genes are expressed in
certain tissues. The proposed research should provide a deeper
understanding of how evolution and development affect gene regulation
thereby increasing our understanding of how perturbations in genetic
regulatory systems can result in human genetic diseases.
StatusFinished
Effective start/end date12/31/893/31/99

Funding

  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences

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