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Field:
Biology/Life Science
Session Topic:
RNA in Systems Biology /Analysis and Synthesis of Mammalian Circadian Clocks
Speaker:
Hiroki R. Ueda/RIKEN
The logic of complex and dynamic biological networks is difficult to elucidate
without (1) comprehensive identification of network structure, (2) prediction and
validation based on quantitative measurement and perturbation of network behavior,
and (3) design and implementation of biological networks driven by the same logic as
the original network. Mammalian circadian clock system is such a system consisting
of complexly integrated regulatory loops and displaying the various dynamic
behaviors including 1) endogenous oscillation with about 24-hour period, 2)
entrainment to the external environmental changes (temperature and light cycle), 3)
temperature compensation over the wide range of temperature, and 4)
synchronization of multiple cellular clocks against the inevitable molecular noise.
To elucidate complex structure and dynamic behavior of mammalian circadian
clock, we comprehensively identify the transcriptional regulatory circuits composed of
20 transcription factors, and three type of DNA elements including “morning” element
(Bmal1/Clock Binding element, E-box/E’-box), “day” element (DBP/E4BP4 binding
element, D-box) and “night” element (RevErbA/ROR binding element, RREs) (Figure
1).
The following quantitative measurement and perturbation of clock circuits
revealed that E-box/E'-box regulation represents a topological and functional
vulnerability in mammalian circadian clocks (Figure 2), and also found the interesting
property of peripheral circadian clocks. In this symposium, we will also report a
current progress in the synthesis of transcriptional circuits underlying mammalian
clock and discuss the logic governing this complex and dynamic biological networks.
References
1.
Ueda, H.R. et al. A transcription factor response element for gene expression
during circadian night. Nature 418, 534-539 (2002).
2. Ueda, H.R. et al. System-level identification of transcription circuit underlying
mammalian circadian clocks. Nat. Genet. 37, 187-192 (2005).
3.
Sato T K, et al. Feedback repression is required for mammalian circadian clock
function. Nat Genet 38:312-9 (2006).
URL
http://www.cdb.riken.jp/jp/02_research/0202_creative20.html
Figure 1. Transcriptional circuits underlying mammalian circadian clocks.
Figure 2. Circadian rhythms in wild-type (a) and mutant cells (b). Mutant cells are impaired
in E-box/E’-box regulation. Each colored line indicates the single-cellular transcriptional
activity while black line indicate the averaged transcriptional activity.