A New Promoter Element Associated with Daily Time Keeping in Drosophila

Sharp, Brandi Alesandro, Department of Biology, University of Virginia
Wijnen, Herman, Department of Biology, University of Virginia
Hirsh, Jay, Department of Biology, University of Virginia
Bekiranov, Stefan, Department of Biochemistry and Molecular Genetics, University of Virginia
Henriksen, Melissa, Applied Research Institute, University of Virginia
Menaker, Michael, Department of Biology, University of Virginia
Pemberton, Lucy, Department of Microbiology, University of Virginia
Schafer, Dorothy, Department of Biology, University of Virginia

Circadian clocks are endogenous daily time keeping mechanisms that allow a wide variety of organisms, including fruit flies and humans, to anticipate Earth's daily environmental rhythms and to organize a daily program of biological functions. The molecular clock of higher eukaryotes consists of highly conserved, interlocking transcription/translation feedback loops which are modulated via rhythmic transcriptional regulation. In core feedback loop of Drosophila melanogaster, the heterodimeric transcription factor CLOCK/CYCLE (CLK/CYC) rhythmically binds E-box regulatory sequences in the promoters of clock-regulated genes. Two core clock genes, PERIOD (PER) and TIMELESS (TIM), dimerize to cyclically repress CLK/CYC-mediated gene expression. The research in this dissertation strives to build our understanding of circadian transcriptional regulation by characterizing a new circadian regulatory sequence. Only a few circadian regulatory sequences have been identified in Drosophila. We have discovered a 29-bp consensus element that, when multimerized, is capable of imparting circadian rhythmicity to a transgenic reporter gene. The element is overrepresented in the promoters of clock and clock-controlled genes and, through interactions with nearby E-box elements, may influence CLK/CYC binding.

Note: Abstract extracted from PDF text

PHD (Doctor of Philosophy)
All rights reserved (no additional license for public reuse)
Issued Date: