Abstract : In mammals, the circadian pacemaker, which controls daily rhythms, is located in the suprachiasmatic nucleus (SCN). Circadian oscillations are generated in individual SCN neurons by a molecular regulatory network. Cells oscillate with periods ranging from 20 to 28 h, but at the tissue level, SCN neurons display significant synchrony, suggesting a robust inter-cellular coupling in which neurotransmitters are assumed to play a crucial role. We present a dynamical model for the coupling of a population of circadian oscillators in the SCN. The cellular oscillator, a three-variable model, describes the core negative feedback loop of the circadian clock. The coupling mechanism is incorporated through the global level of neurotransmitter concentration. Global coupling is efficient to synchronize a population of ten thousand cells. Synchronized cells can be entrained by a 24~h light-dark cycle. Simulations of the interaction between two populations representing two regions of the SCN show that the driven population can be phase leading. Experimentally testable predictions are: (i) Phases of inividual cells are governed by their intrinsic periods. (ii) Efficient synchronization is achieved when the average neurotransmitter concentration would dampen individual oscillators. However, due to the global neurotransmitter oscillation, cells are effectively synchronized.
BACKGROUND: Collections of transcription factor binding profiles (Transfac, Jaspar) are essential to identify regulatory elements
in DNA sequences. Subsets of highly similar profiles complicate large scale analysis of transcription factor binding sites.
METHODS: We propose to identify and group similar profiles using two independent similarity measures: Chi-squared distances between position frequency matrices (PFMs) and correlation coefficients between position weight matrices (PWMs) scores.
RESULTS: We show that these measures complement each other and allow to associate Jaspar and Transfac matrices. Clusters of highly similar matrices are identified and can be used to optimise the search for regulatory elements. Moreover, the application of the measures is illustrated by assigning E-box matrices of a SELEX experiment and of experimentally characterised binding sites of circadian clock genes to the Myc-Max cluster.