Protein arginine methyltransferase 6 controls brythroid Ggene expression and differentiation of human CD34+ progenitor cells

  • Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic activity of recruited chromatin-modifying cofactors. An example is the association of the transcription factor RUNX1 with protein arginine methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However, little is known about the specific influence of PRMT6 on this important branching point. Here, we show that PRMT6 inhibits erythroid gene expression during megakaryopoiesis of primary human CD34+ progenitor cells. PRMT6 is recruited to erythroid genes, such as glycophorin A. Consequently, a repressive histone modification pattern with high H3R2me2a and low H3K4me3 is established. Importantly, inhibition of PRMT6 by shRNA or small molecule inhibitors leads to upregulation of erythroid genes and promotes erythropoiesis. Our data reveal that PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and open up the possibility that manipulation of PRMT6 activity could facilitate enhanced erythropoiesis for therapeutic use.
Author:Stefanie Herkt, Olga Nikolaevna Lausen, Julia Herglotz, Lucas Schneider, Annekarin Meyer, Claudia Pommerenke, Gabriela Salinas-Riester, Erhard SeifriedORCiDGND, Halvard-Björn BönigORCiDGND, Jörn Lausen
Pubmed Id:
Parent Title (English):Haematologica
Publisher:Ferrata Storti Found
Place of publication:Pavia
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/10/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/05/17
Page Number:12
First Page:18
Last Page:29
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Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0