PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.

Protein arginine methyltransferase 4 (PRMT4)-dependent methylation of arginine residues in histones and other chromatin-associated proteins plays an important role in the regulation of gene expression. However, the exact mechanism of how PRMT4 activates transcription remains elusive. Here, we identi...

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Main Authors: Gundula Streubel, Caroline Bouchard, Hannah Berberich, Marc S Zeller, Sophia Teichmann, Jürgen Adamkiewicz, Rolf Müller, Karl-Heinz Klempnauer, Uta-Maria Bauer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3591284?pdf=render
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author Gundula Streubel
Caroline Bouchard
Hannah Berberich
Marc S Zeller
Sophia Teichmann
Jürgen Adamkiewicz
Rolf Müller
Karl-Heinz Klempnauer
Uta-Maria Bauer
author_facet Gundula Streubel
Caroline Bouchard
Hannah Berberich
Marc S Zeller
Sophia Teichmann
Jürgen Adamkiewicz
Rolf Müller
Karl-Heinz Klempnauer
Uta-Maria Bauer
author_sort Gundula Streubel
collection DOAJ
description Protein arginine methyltransferase 4 (PRMT4)-dependent methylation of arginine residues in histones and other chromatin-associated proteins plays an important role in the regulation of gene expression. However, the exact mechanism of how PRMT4 activates transcription remains elusive. Here, we identify the chromatin remodeller Mi2α as a novel interaction partner of PRMT4. PRMT4 binds Mi2α and its close relative Mi2β, but not the other components of the repressive Mi2-containing NuRD complex. In the search for the biological role of this interaction, we find that PRMT4 and Mi2α/β interact with the transcription factor c-Myb and cooperatively coactivate c-Myb target gene expression in haematopoietic cell lines. This coactivation requires the methyltransferase and ATPase activity of PRMT4 and Mi2, respectively. Chromatin immunoprecipitation analysis shows that c-Myb target genes are direct transcriptional targets of PRMT4 and Mi2. Knockdown of PRMT4 or Mi2α/β in haematopoietic cells of the erythroid lineage results in diminished transcriptional induction of c-Myb target genes, attenuated cell growth and survival, and deregulated differentiation resembling the effects caused by c-Myb depletion. These findings reveal an important and so far unknown connection between PRMT4 and the chromatin remodeller Mi2 in c-Myb signalling.
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spelling doaj.art-a7e528087cad46298917476ed0bdf21d2022-12-21T19:18:27ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0193e100334310.1371/journal.pgen.1003343PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.Gundula StreubelCaroline BouchardHannah BerberichMarc S ZellerSophia TeichmannJürgen AdamkiewiczRolf MüllerKarl-Heinz KlempnauerUta-Maria BauerProtein arginine methyltransferase 4 (PRMT4)-dependent methylation of arginine residues in histones and other chromatin-associated proteins plays an important role in the regulation of gene expression. However, the exact mechanism of how PRMT4 activates transcription remains elusive. Here, we identify the chromatin remodeller Mi2α as a novel interaction partner of PRMT4. PRMT4 binds Mi2α and its close relative Mi2β, but not the other components of the repressive Mi2-containing NuRD complex. In the search for the biological role of this interaction, we find that PRMT4 and Mi2α/β interact with the transcription factor c-Myb and cooperatively coactivate c-Myb target gene expression in haematopoietic cell lines. This coactivation requires the methyltransferase and ATPase activity of PRMT4 and Mi2, respectively. Chromatin immunoprecipitation analysis shows that c-Myb target genes are direct transcriptional targets of PRMT4 and Mi2. Knockdown of PRMT4 or Mi2α/β in haematopoietic cells of the erythroid lineage results in diminished transcriptional induction of c-Myb target genes, attenuated cell growth and survival, and deregulated differentiation resembling the effects caused by c-Myb depletion. These findings reveal an important and so far unknown connection between PRMT4 and the chromatin remodeller Mi2 in c-Myb signalling.http://europepmc.org/articles/PMC3591284?pdf=render
spellingShingle Gundula Streubel
Caroline Bouchard
Hannah Berberich
Marc S Zeller
Sophia Teichmann
Jürgen Adamkiewicz
Rolf Müller
Karl-Heinz Klempnauer
Uta-Maria Bauer
PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
PLoS Genetics
title PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
title_full PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
title_fullStr PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
title_full_unstemmed PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
title_short PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
title_sort prmt4 is a novel coactivator of c myb dependent transcription in haematopoietic cell lines
url http://europepmc.org/articles/PMC3591284?pdf=render
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