title: PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.
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 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.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Gundula
authors.initials: G
authors.lastname: Streubel
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouchard
authors.forename: Hannah
authors.initials: H
authors.lastname: Berberich
authors.forename: Marc S
authors.initials: MS
authors.lastname: Zeller
authors.forename: Sophia
authors.initials: S
authors.lastname: Teichmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Adamkiewicz
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Klempnauer
authors.forename: Uta-Maria
authors.initials: UM
authors.lastname: Bauer
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D002843:Chromatin; D006657:Histones; D020598:Proto-Oncogene Proteins c-myb; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex