Protein Arginine Methyltransferase 6 Controls Erythroid Gene Expression and Differentiation of Human CD34 Progenitor Cells

Overview

Journal Haematologica

Specialty Hematology

Date 2017 Oct 14

PMID 29025910

Citations 13

Authors

Stefanie C Herkt

Olga N Kuvardina

Julia Herglotz

Lucas Schneider

Annekarin Meyer

Claudia Pommerenke

Gabriela Salinas-Riester

Erhard Seifried

Halvard Bonig

Jorn Lausen

Affiliations

Soon will be listed here.

Abstract

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 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.

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