title: Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock.
abstract: Interlocked feedback loops may represent a common feature among the regulatory systems controlling circadian rhythms. The Neurospora circadian feedback loops involve white collar-1 (wc-1), wc-2, and frequency (frq) genes. We show that WC-1 and WC-2 proteins activate the transcription of frq gene, whereas FRQ protein plays dual roles: repressing its own transcription, probably by interacting with the WC-1/WC-2 complex, and activating the expression of both WC proteins. Thus, they form two interlocked feedback loops: one negative and one positive. We establish the physiological significance of the interlocked positive feedback loops by showing that the levels of WC-1 and WC-2 determine the robustness and stability of the clock. Our data demonstrate that with WC-1 being the limiting factor in the WC-1/WC-2 complex, the greater the levels of WC-1 and WC-2, the higher the level of the FRQ oscillation and the more robust the overt rhythms. Our data also show that, despite considerable changes in the levels of WC-1, WC-2, and FRQ, the period of the clock has been limited to a small range, suggesting that the interlocked circadian feedback loops are also important for determining the circadian period length of the clock.
authors: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.
authors: P
authors: P
authors: Cheng
authors: Y
authors: Y
authors: Yang
authors: Y
authors: Y
authors: Liu
mesh_terms: D002940:Circadian Rhythm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005246:Feedback; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D005787:Gene Frequency; D009492:Neurospora crassa / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D014157:Transcription Factors; C105589:wc-1 protein, Neurospora crassa; C103772:white collar 2 protein, Neurospora