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SUMMARY:Circadian transcription regulation on long and short timescales
DTSTART:20111201T121500
DTSTAMP:20260920T153711Z
UID:fbce2fbb6cdad7581d2f11046fac0738dbf302e93dcc3475feb7c942
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr Felix Naef\nLife on earth is subjected to daily cycles in l
 ight intensity or temperature. Under such conditions many organisms\, incl
 uding mammals\, evolved a molecular timing device known as the circadian c
 lock\, that controls their daily rhythms in behavior and physiology. These
  cell-autonomous clocks rely on transcriptional feedback loops involving s
 everal key transcription regulators\, that can be studied quantitatively b
 oth on the genome scale using functional genomics approaches\, and on the 
 level of single cells via time-lapse microscopy. To dissect how this netwo
 rk impacts on the temporal organization of molecular processes and cellula
 r functions\, we and others undertook comprehensive analysis of temporal m
 RNA accumulation in mouse liver\, and more recently rhythms in protein-DNA
  interactions or polymerase loadings along the genome. These experiments s
 howed strong interconnections between the clock and metabolic functions of
  the liver\, revealed the dynamic nature of circadian protein-DNA interact
 omes\, and allowed us to model the kinetic relationships between rhythmic 
 transcription and mRNA accumulation. To further scrutinize the molecular o
 scillator in single fibroblast cells\, we exploited a short-lived lucifera
 se reporter to measure the transcriptional activity of circadian and other
  gene promoters at high temporal resolution. We found that transcription o
 ccurs 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\, a
 nd to establish that transcription in mammals is characterized by a refrac
 tory state lasting about one hour. Finally\, fine structure in the burstin
 g patterns of key circadian regulators revealed that rapid bursting at tim
 escales of tens of minutes underlies circadian transcription in mammalian 
 cells.
LOCATION:Sv 1717 A
STATUS:CONFIRMED
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