Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner.
Proc Natl Acad Sci U S A
; 113(41): E6072-E6079, 2016 10 11.
Article
em En
| MEDLINE
| ID: mdl-27688755
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.
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Assunto principal:
Transcrição Gênica
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Regulação da Expressão Gênica
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Regiões Promotoras Genéticas
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Proteínas CLOCK
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Fatores de Transcrição ARNTL
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Criptocromos
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Proteínas Circadianas Period
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article