Title: Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner.

Authors: Chiou, Yi-Ying; Yang, Yanyan; Rashid, Naim; Ye, Rui; Selby, Christopher P; Sancar, Aziz

Published In Proc Natl Acad Sci U S A, (2016 Oct 11)

Abstract: 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.

PubMed ID: 27688755

MeSH Terms: ARNTL Transcription Factors/genetics; ARNTL Transcription Factors/metabolism*; Active Transport, Cell Nucleus; Alleles; Animals; Binding Sites; CLOCK Proteins/genetics; CLOCK Proteins/metabolism*; Cell Line; Cryptochromes/metabolism*; E-Box Elements; Fibroblasts/metabolism; Gene Expression Regulation*; Gene Knockout Techniques; Genetic Loci; Mice; Models, Biological; Mutation; Nucleotide Motifs; Period Circadian Proteins/metabolism*; Promoter Regions, Genetic*; Protein Binding; Protein Biosynthesis; Trans-Activators/metabolism; Transcription, Genetic*