PER2 mediates CREB-dependent light induction of the clock gene Per1

Abstract Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 1...

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Autores principales:	Andrea Brenna, Jürgen A. Ripperger, Gabriella Saro, Dominique A. Glauser, Zhihong Yang, Urs Albrecht
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/55972a9e089a48e880f4e74241171cbb
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spelling	oai:doaj.org-article:55972a9e089a48e880f4e74241171cbb2021-11-08T10:54:12ZPER2 mediates CREB-dependent light induction of the clock gene Per110.1038/s41598-021-01178-62045-2322https://doaj.org/article/55972a9e089a48e880f4e74241171cbb2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01178-6https://doaj.org/toc/2045-2322Abstract Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1). However, the details of this pathway are poorly understood. Here we provide evidence that PER2 acts as a co-factor of CREB to facilitate the formation of a transactivation complex on the CRE element of the Per1 gene regulatory region in response to light or forskolin. Using in vitro and in vivo approaches, we show that PER2 modulates the interaction between CREB and its co-regulator CRTC1 to support complex formation only after a light or forskolin stimulus. Furthermore, the absence of PER2 abolished the interaction between the histone acetyltransferase CBP and CREB. This process was accompanied by a reduction of histone H3 acetylation and decreased recruitment of RNA Pol II to the Per1 gene. Collectively, our data show that PER2 supports the stimulus-dependent induction of the Per1 gene via modulation of the CREB/CRTC1/CBP complex.Andrea BrennaJürgen A. RippergerGabriella SaroDominique A. GlauserZhihong YangUrs AlbrechtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea Brenna Jürgen A. Ripperger Gabriella Saro Dominique A. Glauser Zhihong Yang Urs Albrecht PER2 mediates CREB-dependent light induction of the clock gene Per1
description	Abstract Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1). However, the details of this pathway are poorly understood. Here we provide evidence that PER2 acts as a co-factor of CREB to facilitate the formation of a transactivation complex on the CRE element of the Per1 gene regulatory region in response to light or forskolin. Using in vitro and in vivo approaches, we show that PER2 modulates the interaction between CREB and its co-regulator CRTC1 to support complex formation only after a light or forskolin stimulus. Furthermore, the absence of PER2 abolished the interaction between the histone acetyltransferase CBP and CREB. This process was accompanied by a reduction of histone H3 acetylation and decreased recruitment of RNA Pol II to the Per1 gene. Collectively, our data show that PER2 supports the stimulus-dependent induction of the Per1 gene via modulation of the CREB/CRTC1/CBP complex.
format	article
author	Andrea Brenna Jürgen A. Ripperger Gabriella Saro Dominique A. Glauser Zhihong Yang Urs Albrecht
author_facet	Andrea Brenna Jürgen A. Ripperger Gabriella Saro Dominique A. Glauser Zhihong Yang Urs Albrecht
author_sort	Andrea Brenna
title	PER2 mediates CREB-dependent light induction of the clock gene Per1
title_short	PER2 mediates CREB-dependent light induction of the clock gene Per1
title_full	PER2 mediates CREB-dependent light induction of the clock gene Per1
title_fullStr	PER2 mediates CREB-dependent light induction of the clock gene Per1
title_full_unstemmed	PER2 mediates CREB-dependent light induction of the clock gene Per1
title_sort	per2 mediates creb-dependent light induction of the clock gene per1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/55972a9e089a48e880f4e74241171cbb
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PER2 mediates CREB-dependent light induction of the clock gene Per1

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