Circadian transcription regulation on long and short timescales
Event details
| Date | 01.12.2011 |
| Hour | 12:15 |
| Speaker | Dr Felix Naef |
| Location |
Sv 1717 A
|
| Category | Conferences - Seminars |
Life on earth is subjected to daily cycles in light intensity or temperature. Under such conditions many organisms, including mammals, evolved a molecular timing device known as the circadian clock, that controls their daily rhythms in behavior and physiology. These cell-autonomous clocks rely on transcriptional feedback loops involving several key transcription regulators, that can be studied quantitatively both on the genome scale using functional genomics approaches, and on the level of single cells via time-lapse microscopy. To dissect how this network impacts on the temporal organization of molecular processes and cellular functions, we and others undertook comprehensive analysis of temporal mRNA accumulation in mouse liver, and more recently rhythms in protein-DNA interactions or polymerase loadings along the genome. These experiments showed strong interconnections between the clock and metabolic functions of the liver, revealed the dynamic nature of circadian protein-DNA interactomes, and allowed us to model the kinetic relationships between rhythmic transcription and mRNA accumulation. To further scrutinize the molecular oscillator in single fibroblast cells, we exploited a short-lived luciferase reporter to measure the transcriptional activity of circadian and other gene promoters at high temporal resolution. We found that transcription occurs discontinuously, i.e. it switches stochastically between short and intensive intervals of mRNA synthesis, called bursts, followed by longer periods of silence. A novel mathematical analysis of the temporal signals allowed us to discover how bursting patterns are highly gene specific, and to establish that transcription in mammals is characterized by a refractory state lasting about one hour. Finally, fine structure in the bursting patterns of key circadian regulators revealed that rapid bursting at timescales of tens of minutes underlies circadian transcription in mammalian cells.
Practical information
- General public
- Free
Contact
- M. Mary / H. Hirling