PRMT4 Is a Novel Coactivator of c-Myb-Dependent Transcription in Haematopoietic Cell Lines
Citation:
Streubel,Gundula G., Bouchard,Caroline S. C.S., Berberich,Hannah H., Zeller,Marc S. M.S., Teichmann,Sophia S., Adamkiewicz,Jürgen J., Müller,Rolf Joachim R.J., Klempnauer,Karl Heinz K.H., Bauer,Uta Maria U.M., PRMT4 Is a Novel Coactivator of c-Myb-Dependent Transcription in Haematopoietic Cell Lines, PLoS Genetics, 9, 3, 2013Download Item:
Abstract:
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 Mi2
a
as a novel interaction
partner of PRMT4. PRMT4 binds Mi2
a
and its close relative Mi2
b
, 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 Mi2
a
/
b
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 Mi2
a
/
b
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.
Author's Homepage:
http://people.tcd.ie/streubegDescription:
PUBLISHED
Author: STREUBEL, GUNDULA
Type of material:
Journal ArticleCollections
Series/Report no:
PLoS Genetics9
3
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Full text availableKeywords:
c-Myb target genesDOI:
http://dx.doi.org/10.1371/journal.pgen.1003343ISSN:
15537390Metadata
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