Differential context-specific impact of individual core promoter elements on transcriptional dynamics.

Hendy, Oliver; Campbell, John; Weissman, Jocelyn D; Larson, Daniel R; Singer, Dinah S

Hendy, Oliver; Campbell, John; Weissman, Jocelyn D; Larson, Daniel R; Singer, Dinah S.

Afiliación

Hendy O; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Campbell J; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Weissman JD; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Larson DR; Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Singer DS; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Dinah.Singer@nih.gov.

Mol Biol Cell ; 28(23): 3360-3370, 2017 Nov 07.

Article en En | MEDLINE | ID: mdl-28931597

RESUMEN

Eukaryotic transcription occurs in bursts that vary in size and frequency, but the contribution of individual core promoter elements to transcriptional bursting is not known. Here we analyze the relative contributions to bursting of the individual core promoter elements-CCAAT, TATAA-like, Sp1BS, and Inr-of an MHC class I gene in primary B-cells during both basal and activated transcription. The TATAA-like, Sp1BS, and Inr elements all function as negative regulators of transcription, and each was found to contribute differentially to the overall bursting pattern of the promoter during basal transcription. Whereas the Sp1BS element regulates burst size, the Inr element regulates burst frequency. The TATAA-like element contributes to both. Surprisingly, each element has a distinct role in bursting during transcriptional activation by Î³-interferon. The CCAAT element does not contribute significantly to the constitutive transcriptional dynamics of primary B-cells, but modulates both burst size and frequency in response to Î³-interferon activation. The ability of core promoter elements to modulate transcriptional bursting individually allows combinatorial fine-tuning of the level of MHC class I gene expression in response to intrinsic and extrinsic signals.

Asunto(s)

Regulación de la Expresión Génica/genética; Regiones Promotoras Genéticas/fisiología; Activación Transcripcional/genética; Linfocitos B; Humanos; Interferón gamma/metabolismo; Regiones Promotoras Genéticas/genética; Transactivadores/metabolismo; Factores de Transcripción/metabolismo; Transcripción Genética/genética; Activación Transcripcional/fisiología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación Transcripcional / Regulación de la Expresión Génica / Regiones Promotoras Genéticas Límite: Humans Idioma: En Revista: Mol Biol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos

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