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Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo

Activity-dependent alteration of the transcriptional program is central for shaping neuronal connectivity. Constitutively expressed transcription factors orchestrate the initial response to neuronal stimulation and serve as substrates for second messenger-regulated kinase signalling cascades. The mi...

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Autores principales: Blüthgen, Nils, van Bentum, Mirjam, Merz, Barbara, Kuhl, Dietmar, Hermey, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368636/
https://www.ncbi.nlm.nih.gov/pubmed/28349920
http://dx.doi.org/10.1038/srep45101
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author Blüthgen, Nils
van Bentum, Mirjam
Merz, Barbara
Kuhl, Dietmar
Hermey, Guido
author_facet Blüthgen, Nils
van Bentum, Mirjam
Merz, Barbara
Kuhl, Dietmar
Hermey, Guido
author_sort Blüthgen, Nils
collection PubMed
description Activity-dependent alteration of the transcriptional program is central for shaping neuronal connectivity. Constitutively expressed transcription factors orchestrate the initial response to neuronal stimulation and serve as substrates for second messenger-regulated kinase signalling cascades. The mitogen-activated protein kinase ERK conveys signalling from the synapse to the nucleus but its genetic signature following neuronal activity has not been revealed. The goal of the present study was to identify ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus. We used generalized seizures combined with the pharmacological intervention of MEK activation as an in vivo model to determine the complete transcriptional program initiated by ERK after neuronal activity. Our survey demonstrates that the induction of a large number of activity-regulated genes, including Arc/Arg3.1, Arl5b, Gadd45b, Homer1, Inhba and Zwint, is indeed dependent on ERK phosphorylation. In contrast, expression of a small group of genes, including Npas4, Arl4d, Errfi1, and Rgs2, is only partially dependent or completely independent (Ppp1r15a) of this signalling pathway. Among the identified transcripts are long non-coding (lnc) RNAs and induction of LincPint and splice variants of NEAT1 are ERK dependent. Our survey provides a comprehensive analysis of the transcriptomic response conveyed by ERK signalling in the hippocampus.
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spelling pubmed-53686362017-03-30 Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo Blüthgen, Nils van Bentum, Mirjam Merz, Barbara Kuhl, Dietmar Hermey, Guido Sci Rep Article Activity-dependent alteration of the transcriptional program is central for shaping neuronal connectivity. Constitutively expressed transcription factors orchestrate the initial response to neuronal stimulation and serve as substrates for second messenger-regulated kinase signalling cascades. The mitogen-activated protein kinase ERK conveys signalling from the synapse to the nucleus but its genetic signature following neuronal activity has not been revealed. The goal of the present study was to identify ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus. We used generalized seizures combined with the pharmacological intervention of MEK activation as an in vivo model to determine the complete transcriptional program initiated by ERK after neuronal activity. Our survey demonstrates that the induction of a large number of activity-regulated genes, including Arc/Arg3.1, Arl5b, Gadd45b, Homer1, Inhba and Zwint, is indeed dependent on ERK phosphorylation. In contrast, expression of a small group of genes, including Npas4, Arl4d, Errfi1, and Rgs2, is only partially dependent or completely independent (Ppp1r15a) of this signalling pathway. Among the identified transcripts are long non-coding (lnc) RNAs and induction of LincPint and splice variants of NEAT1 are ERK dependent. Our survey provides a comprehensive analysis of the transcriptomic response conveyed by ERK signalling in the hippocampus. Nature Publishing Group 2017-03-28 /pmc/articles/PMC5368636/ /pubmed/28349920 http://dx.doi.org/10.1038/srep45101 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Blüthgen, Nils
van Bentum, Mirjam
Merz, Barbara
Kuhl, Dietmar
Hermey, Guido
Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title_full Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title_fullStr Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title_full_unstemmed Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title_short Profiling the MAPK/ERK dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
title_sort profiling the mapk/erk dependent and independent activity regulated transcriptional programs in the murine hippocampus in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368636/
https://www.ncbi.nlm.nih.gov/pubmed/28349920
http://dx.doi.org/10.1038/srep45101
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