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The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation

Protein arginine methyltransferases (PRMT) have been implicated in the regulation of transcription. They are recruited to promoters via interaction with transcription factors and exert their coactivator function by methylating arginine residues in histones and other chromatin proteins. Here, we empl...

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Autores principales: Kleinschmidt, Markus A., Streubel, Gundula, Samans, Birgit, Krause, Michael, Bauer, Uta-Maria
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425501/
https://www.ncbi.nlm.nih.gov/pubmed/18413343
http://dx.doi.org/10.1093/nar/gkn166
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author Kleinschmidt, Markus A.
Streubel, Gundula
Samans, Birgit
Krause, Michael
Bauer, Uta-Maria
author_facet Kleinschmidt, Markus A.
Streubel, Gundula
Samans, Birgit
Krause, Michael
Bauer, Uta-Maria
author_sort Kleinschmidt, Markus A.
collection PubMed
description Protein arginine methyltransferases (PRMT) have been implicated in the regulation of transcription. They are recruited to promoters via interaction with transcription factors and exert their coactivator function by methylating arginine residues in histones and other chromatin proteins. Here, we employ an unbiased approach to identify novel target genes, which are under the control of two members of the enzyme family, PRMT1 and CARM1/PRMT4 (coactivator associated arginine methyltransferase 1). By using cDNA microarray analysis, we find that the siRNA-mediated single knockdown of neither CARM1 nor PRMT1 causes significant changes in gene expression. In contrast, double knockdown of both enzymes results in the deregulated expression of a large group of genes, among them the CITED2 gene. Cytokine-stimulated expression analysis indicates that transcriptional activation of CITED2 depends on STAT5 and the coactivation of both PRMTs. ChIP analysis identifies the CITED2 gene as a direct target gene of STAT5, CARM1 and PRMT1. In reporter gene assays, we show that STAT5-mediated transcription is cooperatively enhanced by CARM1 and PRMT1. Interaction assays reveal a cytokine-induced association of STAT5 and the two PRMTs. Our data demonstrate a widespread cooperation of CARM1 and PRMT1 in gene activation as well as repression and that STAT5-dependent transcription of the CITED2 gene is a novel pathway coactivated by the two methyltransferases.
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spelling pubmed-24255012008-06-12 The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation Kleinschmidt, Markus A. Streubel, Gundula Samans, Birgit Krause, Michael Bauer, Uta-Maria Nucleic Acids Res Molecular Biology Protein arginine methyltransferases (PRMT) have been implicated in the regulation of transcription. They are recruited to promoters via interaction with transcription factors and exert their coactivator function by methylating arginine residues in histones and other chromatin proteins. Here, we employ an unbiased approach to identify novel target genes, which are under the control of two members of the enzyme family, PRMT1 and CARM1/PRMT4 (coactivator associated arginine methyltransferase 1). By using cDNA microarray analysis, we find that the siRNA-mediated single knockdown of neither CARM1 nor PRMT1 causes significant changes in gene expression. In contrast, double knockdown of both enzymes results in the deregulated expression of a large group of genes, among them the CITED2 gene. Cytokine-stimulated expression analysis indicates that transcriptional activation of CITED2 depends on STAT5 and the coactivation of both PRMTs. ChIP analysis identifies the CITED2 gene as a direct target gene of STAT5, CARM1 and PRMT1. In reporter gene assays, we show that STAT5-mediated transcription is cooperatively enhanced by CARM1 and PRMT1. Interaction assays reveal a cytokine-induced association of STAT5 and the two PRMTs. Our data demonstrate a widespread cooperation of CARM1 and PRMT1 in gene activation as well as repression and that STAT5-dependent transcription of the CITED2 gene is a novel pathway coactivated by the two methyltransferases. Oxford University Press 2008-06 2008-04-15 /pmc/articles/PMC2425501/ /pubmed/18413343 http://dx.doi.org/10.1093/nar/gkn166 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Kleinschmidt, Markus A.
Streubel, Gundula
Samans, Birgit
Krause, Michael
Bauer, Uta-Maria
The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title_full The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title_fullStr The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title_full_unstemmed The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title_short The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation
title_sort protein arginine methyltransferases carm1 and prmt1 cooperate in gene regulation
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425501/
https://www.ncbi.nlm.nih.gov/pubmed/18413343
http://dx.doi.org/10.1093/nar/gkn166
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