Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function

Most clock genes encode transcription factors that interact to elicit coope rative control of clock function. Using a two-hybrid system approach, we ha ve isolated two different partners of zebrafish (zf) CLOCK, which are simil ar to the mammalian BMAL1 (brain and muscle arylhydrocarbon receptor nuclea r translocator-like protein 1), The two homologs, zfBMAL1 and zfBMAL2, cont ain conserved basic helix-loop-helix-PAS (Period-Arylhydrocarbon receptor-S ingleminded) domains but diverge in the carboxyl termini, thus bearing diff erent transcriptional activation potential. As for zf-Clock, the expression of both zfBmals oscillates in most tissues in the animal. However, in many tissues, the peak, levels, and kinetics of expression are different betwee n the two genes and for the same gene from tissue to tissue. These results support the existence of independent peripheral oscillators and suggest tha t zfBMAL1 and zfBMAL2 may exert distinct circadian functions, interacting d ifferentially with zfCLOCK at various times in different tissues. Our findi ngs also indicate that multiple controls may be exerted by the central cloc k and/or that peripheral oscillators can differentially interpret central c lock signals.