Transcriptional regulation and function of the Neurospora clock gene white collar 2 and its isoforms.

FREQUENCY (FRQ) and the White Collar Complex (WCC), consisting of WC1 and WC2 subunits, are crucial components of positive and negative feedback loops of the circadian clock of Neurospora. In the positive limb, FRQ supports the accumulation of WC1 on a post-translational level and activates transcription of wc2. We analysed the transcriptional regulation of wc2. The WCC indirectly inhibits wc2 by controlling expression of a putative repressor. FRQ activates wc2 transcription by inhibiting WCC. A putative transcriptional activator binds to the wc2 promoter and antagonizes the repressor function. Furthermore, an internal promoter in the wc2 coding region drives expression of an amino-terminally shortened isoform, sWC2. Full-length WC2 and sWC2 are expressed in an antagonistic manner; thus, sWC2 expression seems to be a fail-safe mechanism that maintains total WC2 levels above a threshold.