Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner.
The mammalian circadian clock is based on a transcription-translation feedback loop (TTFL) consolidated by secondary loops. In the primary TTFL, the circadian locomotor output cycles kaput (CLOCK)-brain and muscle Arnt-like protein-1 (BMAL1) heterodimer acts as the transcriptional activator, and Cryptochrome (CRY) and Period (PER) proteins function as repressors. PER represses by displacing CLOCK-BMAL1 from promoters in a CRY-dependent manner. Interestingly, genes with complex promoters may either be repressed or de-repressed by PER, depending on the particular promoter regulatory elements. Here, using mouse cell lines with defined knockout mutations in clock genes, RNA-seq, ChIP-seq, and reporter gene assays coupled with measurements of DNA-protein interactions in nuclear extracts, we elucidate the dual functions of PER as repressor and de-repressor in a context-dependent manner.
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
Yi-Ying
YY
Chiou
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
Yanyan
Y
Yang
Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599.
Naim
N
Rashid
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
Rui
R
Ye
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
Christopher P
CP
Selby
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 aziz_sancar@med.unc.edu.
Aziz
A
Sancar
D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000483:Alleles; D000818:Animals; D001665:Binding Sites; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D056931:Cryptochromes / Q000378:metabolism*; D024721:E-Box Elements; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D056426:Genetic Loci; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D059372:Nucleotide Motifs; D056950:Period Circadian Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D056931:Cryptochromes; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D015534:Trans-Activators; D056926:CLOCK Proteins
DNA binding; Period; activator; circadian; transcription
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