The molecular circadian clock in mammals is generated from transcriptional 
activation by the bHLH-PAS transcription factor CLOCK-BMAL1 and subsequent 
repression by PERIOD and CRYPTOCHROME (CRY). The mechanism by which CRYs repress 
CLOCK-BMAL1 to close the negative feedback loop and generate 24-h timing is not 
known. Here we show that, in mouse fibroblasts, CRY1 competes for binding with 
coactivators to the intrinsically unstructured C-terminal transactivation domain 
(TAD) of BMAL1 to establish a functional switch between activation and 
repression of CLOCK-BMAL1. TAD mutations that alter affinities for co-regulators 
affect the balance of repression and activation to consequently change the 
intrinsic circadian period or eliminate cycling altogether. Our results suggest 
that CRY1 fulfills its role as an essential circadian repressor by sequestering 
the TAD from coactivators, and they highlight regulation of the BMAL1 TAD as a 
critical mechanism for establishing circadian timing.