FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs

Abstract Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have u...

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Autores principales:	Billie G. C. Griffith, Rosanna Upstill-Goddard, Holly Brunton, Graeme R. Grimes, Andrew V. Biankin, Bryan Serrels, Adam Byron, Margaret C. Frame
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/164998aec79f4674b257ec55ae3e2b20
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spelling	oai:doaj.org-article:164998aec79f4674b257ec55ae3e2b202021-12-02T15:13:10ZFAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs10.1038/s41598-020-80111-92045-2322https://doaj.org/article/164998aec79f4674b257ec55ae3e2b202021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80111-9https://doaj.org/toc/2045-2322Abstract Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on the Il33 gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulates Il33 gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression.Billie G. C. GriffithRosanna Upstill-GoddardHolly BruntonGraeme R. GrimesAndrew V. BiankinBryan SerrelsAdam ByronMargaret C. FrameNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Billie G. C. Griffith Rosanna Upstill-Goddard Holly Brunton Graeme R. Grimes Andrew V. Biankin Bryan Serrels Adam Byron Margaret C. Frame FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
description	Abstract Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on the Il33 gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulates Il33 gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression.
format	article
author	Billie G. C. Griffith Rosanna Upstill-Goddard Holly Brunton Graeme R. Grimes Andrew V. Biankin Bryan Serrels Adam Byron Margaret C. Frame
author_facet	Billie G. C. Griffith Rosanna Upstill-Goddard Holly Brunton Graeme R. Grimes Andrew V. Biankin Bryan Serrels Adam Byron Margaret C. Frame
author_sort	Billie G. C. Griffith
title	FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
title_short	FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
title_full	FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
title_fullStr	FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
title_full_unstemmed	FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
title_sort	fak regulates il-33 expression by controlling chromatin accessibility at c-jun motifs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/164998aec79f4674b257ec55ae3e2b20
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FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs

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