ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription

We investigated the relationship among ERK signaling, histone modifications, and transcription factor activity, focusing on the ERK-regulated ternary complex factor family of SRF partner proteins. In MEFs, activation of ERK by TPA stimulation induced a common pattern of H3K9acS10ph, H4K16ac, H3K27ac...

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Autores principales: Esnault, Cyril, Gualdrini, Francesco, Horswell, Stuart, Kelly, Gavin, Stewart, Aengus, East, Phil, Matthews, Nik, Treisman, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364370/
https://www.ncbi.nlm.nih.gov/pubmed/28286024
http://dx.doi.org/10.1016/j.molcel.2017.02.005
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author Esnault, Cyril
Gualdrini, Francesco
Horswell, Stuart
Kelly, Gavin
Stewart, Aengus
East, Phil
Matthews, Nik
Treisman, Richard
author_facet Esnault, Cyril
Gualdrini, Francesco
Horswell, Stuart
Kelly, Gavin
Stewart, Aengus
East, Phil
Matthews, Nik
Treisman, Richard
author_sort Esnault, Cyril
collection PubMed
description We investigated the relationship among ERK signaling, histone modifications, and transcription factor activity, focusing on the ERK-regulated ternary complex factor family of SRF partner proteins. In MEFs, activation of ERK by TPA stimulation induced a common pattern of H3K9acS10ph, H4K16ac, H3K27ac, H3K9acK14ac, and H3K4me3 at hundreds of transcription start site (TSS) regions and remote regulatory sites. The magnitude of the increase in histone modification correlated well with changes in transcription. H3K9acS10ph preceded the other modifications. Most induced changes were TCF dependent, but TCF-independent TSSs exhibited the same hierarchy, indicating that it reflects gene activation per se. Studies with TCF Elk-1 mutants showed that TCF-dependent ERK-induced histone modifications required Elk-1 to be phosphorylated and competent to activate transcription. Analysis of direct TCF-SRF target genes and chromatin modifiers confirmed this and showed that H3S10ph required only Elk-1 phosphorylation. Induction of histone modifications following ERK stimulation is thus directed by transcription factor activation and transcription.
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spelling pubmed-53643702017-03-31 ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription Esnault, Cyril Gualdrini, Francesco Horswell, Stuart Kelly, Gavin Stewart, Aengus East, Phil Matthews, Nik Treisman, Richard Mol Cell Article We investigated the relationship among ERK signaling, histone modifications, and transcription factor activity, focusing on the ERK-regulated ternary complex factor family of SRF partner proteins. In MEFs, activation of ERK by TPA stimulation induced a common pattern of H3K9acS10ph, H4K16ac, H3K27ac, H3K9acK14ac, and H3K4me3 at hundreds of transcription start site (TSS) regions and remote regulatory sites. The magnitude of the increase in histone modification correlated well with changes in transcription. H3K9acS10ph preceded the other modifications. Most induced changes were TCF dependent, but TCF-independent TSSs exhibited the same hierarchy, indicating that it reflects gene activation per se. Studies with TCF Elk-1 mutants showed that TCF-dependent ERK-induced histone modifications required Elk-1 to be phosphorylated and competent to activate transcription. Analysis of direct TCF-SRF target genes and chromatin modifiers confirmed this and showed that H3S10ph required only Elk-1 phosphorylation. Induction of histone modifications following ERK stimulation is thus directed by transcription factor activation and transcription. Cell Press 2017-03-16 /pmc/articles/PMC5364370/ /pubmed/28286024 http://dx.doi.org/10.1016/j.molcel.2017.02.005 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Esnault, Cyril
Gualdrini, Francesco
Horswell, Stuart
Kelly, Gavin
Stewart, Aengus
East, Phil
Matthews, Nik
Treisman, Richard
ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title_full ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title_fullStr ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title_full_unstemmed ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title_short ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
title_sort erk-induced activation of tcf family of srf cofactors initiates a chromatin modification cascade associated with transcription
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364370/
https://www.ncbi.nlm.nih.gov/pubmed/28286024
http://dx.doi.org/10.1016/j.molcel.2017.02.005
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