title: ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription.
abstract: 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.
authors.affiliation: Signalling and Transcription Group, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Cyril
authors.initials: C
authors.lastname: Esnault
authors.affiliation: Signalling and Transcription Group, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gualdrini
authors.affiliation: Bioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Horswell
authors.affiliation: Bioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Bioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Aengus
authors.initials: A
authors.lastname: Stewart
authors.affiliation: Bioinformatics and Biostatistics STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: East
authors.affiliation: Advanced Sequencing STP, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Nik
authors.initials: N
authors.lastname: Matthews
authors.affiliation: Signalling and Transcription Group, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: richard.treisman@crick.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Treisman
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010766:Phosphorylation; D034622:RNA Interference; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C494113:Elk1 protein, mouse; D006657:Histones; D026362:Serum Response Factor; D051820:TCF Transcription Factors; D050807:ets-Domain Protein Elk-1; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: ERK; Elk-1; H3 phosphorylation; SRF; chromatin; histone modification; immediate-early genes; ternary complex factor; transcription