Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin-remodeling enzyme CLOCKSWITCH.
In the Neurospora circadian system, the transcription factors White Collar-1 (WC-1) and White Collar-2 (WC-2) activate expression of frq, whose gene product inhibits its own expression. The WC proteins are thought to form an obligate complex; however, chromatin immunoprecipitation (ChIP) indicates that WC-2 binds to the frq promoter in a rhythmic fashion, whereas WC-1 is bound continuously. Small oscillations in histone acetylation are detected over the circadian cycle with a marked reduction upon light-induced activation. Nuclease accessibility experiments indicate chromatin rearrangement at the frq promoter; therefore, 19 genes with homology to ATP-dependent chromatin-remodeling enzymes were deleted and the strains examined for clock phenotypes. One gene, designated clockswitch (csw-1), is required for clock function; its product localizes to the frq promoter, is required for proper frq expression, and has an impact on chromatin structure. The data suggest that CSW-1 regulates accessibility of promoter DNA, thus generating the sharp transition from the transcriptionally active to the repressed state.
Belden
William J
WJ
Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Loros
Jennifer J
JJ
Dunlap
Jay C
JC
D000107:Acetylation; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002940:Circadian Rhythm; D004271:DNA, Fungal / Q000378:metabolism; D025461:Feedback, Physiological; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006657:Histones / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009492:Neurospora crassa / Q000201:enzymology* / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology
D002843:Chromatin; D004271:DNA, Fungal; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D006657:Histones; D012333:RNA, Messenger; D000255:Adenosine Triphosphate