Molecular “Double Switch” Operates Biological Clock
Posted January 09 2012
Heidelberg researchers resolve daytime-based activation of genes

Researchers of the Heidelberg Cluster of Excellence CellNetworks identified a “molecular double-switch” that enables the biological clock of Neurospora to optimally adjust to day and night. The project was led by scientists of the Heidelberg University Biochemisty Center (BZH). The findings indicate that a “morning-specific clock protein”, the transcription factor White Collar Complex (WCC), “switches on” around 400 genes before sunrise. One of these morning-specific genes triggers the immediate production of a gene repressor, which “switches off” another group of about 800 “evening-specific genes” in the morning, that are expressed during the night. In the course of a day the morning-specific activator is turned off and the repressor degraded. Accordingly, by the end of the day, morning-specific genes are switched off and the evening-specific genes are switched on. The results of the research were published in the journal “Molecular Cell”.


Biological clocks are molecular pacemakers, which are found in the cells of almost every living organism where they adjust metabolism and behavior according to the time of the day. Since even in constant darkness this molecular clock is able to oscillate with a period of nearly 24 h it is also called “circadian clock” (circa dian = about a day). Depending on the time of day the clock switches on or off a large number of genes. So-called “Zeitgeber”, environmental signals such as light, help to synchronize the circadian clock. The sleep-wake cycle, for instance, is largely controlled by the circadian clock. In fact, jetlags that occur after travels across time zones are caused by a time discrepancy between the internal and external time. Until recently it was unclear how circadian clocks differentially switch sets of genes on and off at different times of day.


In cooperation with scientists from the BZH and BioQuant the research group of Prof. Dr. Michael Brunner was able to answer this question. The filamentous fungus Neurospora crassa was used as a model organism to investigate the circadian clock at a molecular level. The project involved state-of-the-art technology provided by the CellNetworks research cluster, which is funded by the German Excellence Initiative. In particular transcriptome analysis by next-generation sequencing and detailed molecular analysis of the composition of cell membranes by quantitative lipid mass spectrometry were crucial for the work.


In the core of the Neurospora circadian system is the transcription factor WCC, a protein complex that is directly or indirectly responsible for switching on or off more than 1,000 genes dependent on the time of the day. The WCC contains a special light-sensitive “switch” (LOV domain), which allows synchronizing the internal time with the external time set by the rotation of the earth. Genes directly regulated by the WCC are active in the morning. One of these genes encodes the transcription repressor CSP1, which switches off genes in the morning that were active during the night. Among other functions, CSP1 regulates the composition of the cell membrane. During the day, when temperature rises, the membrane becomes more rigid and during the cooler night it becomes more fluid. This ensures an optimal exchange of substances across the cell membrane at all times.


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Prof. Dr. Michael Brunner
der Universität Heidelberg (BZH)
Phone (06221) 54-4207
michael.brunner [ aT ]