A Global Circadian Repressor Controls Antiphasic Expression of Metabolic Genes in Neurospora

SummaryThe white-collar complex (WCC), the core transcription factor of the circadian clock of Neurospora, activates morning-specific expression of the transcription repressor CSP1. Newly synthesized CSP1 exists in a transient complex with the corepressor RCM1/RCO1 and the ubiquitin ligase UBR1. CSP1 is rapidly hyperphosphorylated and degraded via UBR1 and its ubiquitin conjugase RAD6. Genes controlled by CSP1 are rhythmically expressed and peak in the evening (i.e., in antiphase to morning-specific genes directly controlled by WCC). Rhythmic expression of these second-tier genes depends crucially on phosphorylation and rapid turnover of CSP1, which ensures tight coupling of CSP1 abundance and function to the circadian activity of WCC. Negative feedback of CSP1 on its own transcription buffers the amplitude of CSP1-dependent oscillations against fluctuations of WCC activity. CSP1 predominantly regulates genes involved in metabolism. It controls ergosterol synthesis and fatty acid desaturases and thereby modulates the lipid composition of membranes.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (207 K)Download as PowerPoint slideHighlights► The transcription repressor CSP1 controls output of the Neurospora circadian clock ► CSP1 interacts transiently with the corepressor RCM1/RCO1 and the E3 ligase UBR1 ► CSP1 is a morning-specific repressor of evening-specific genes ► CSP1 controls the lipid composition of membranes