A New Promoter Element Associated with Daily Time Keeping in Drosophila

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.

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