Ukai-Tadenuma, Maki Yamada, Rikuhiro G. Xu, Haiyan Ripperger, Jürgen A. Liu, Andrew C. Ueda, Hiroki R. 2011-01-13 Direct evidence for the requirement of delay in feedback repression in the mammalian circadian clock has been elusive. <i>Cryptochrome 1</i> (<i>Cry1</i>), an essential clock component, displays evening-time expression and serves as a strong repressor at morning-time elements (E box/E<strong>′</strong> box). In this study, we reveal that a combination of day-time elements (D box) within the <i>Cry1</i>-proximal promoter and night-time elements (RREs) within its intronic enhancer gives rise to evening-time expression. A synthetic composite promoter produced evening-time expression, which was further recapitulated by a simple phase-vector model. Of note, coordination of day-time with night-time elements can modulate the extent of phase delay. A genetic complementation assay in <i>Cry1</i>^−/−:<i>Cry2</i>^−/− cells revealed that substantial delay of <i>Cry1</i> expression is required to restore circadian rhythmicity, and its prolonged delay slows circadian oscillation. Taken together, our data suggest that phase delay in <i>Cry1</i> transcription is required for mammalian clock function. application/pdf https://folia.unifr.ch/global/documents/301731 https://folia.unifr.ch/documents/301731/files/rip_dfr.pdf https://folia.unifr.ch/documents/301731/files/rip_dfr_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2010.12.019 info:eu-repo/semantics/openAccess License undefined Cell. - 2011, vol. 144, no. 2, p. 268-281 info:eu-repo/classification/udc/57 Delay in feedback repression by Cryptochrome 1 is required for circadian clock function http://purl.org/coar/resource_type/c_6501