Contributions of the Histone Arginine Methyltransferase PRMT6 to the Epigenetic Function of RUNX1

Abstract

Hematopoietic differentiation is directed by transcription factors such as RUNX1. RUNX1 binds to specific DNA binding sites in regulatory elements of genes and recruits epigenetic cofactors to target loci. In this way histone modification patterns and the chromatin environment are altered, which results in adjusted gene expression. The process of transcription factor binding and cofactor recruitment is dynamic and strongly influenced by specific posttranslational modifications, which are triggered by signaling. In this way cellular signaling is integrated at the epigenetic level by transcription factors. The identification of epigenetic cofactors and the study of their epigenetic influence on transcription is crucial for the understanding of transcription factor function in differentiation and disease. In this article, the recent observation that RUNX1 is associated with the protein arginine methyltransferase 6 will be reviewed. PRMT6 triggers H3R2me2a at RUNX1 target genes; this histone modification negatively influences the positive H3K4me3 mark and this way acts repressive. The RUNX1/PRMT6 association has an impact on bivalent histone marks. Upon differentiation, a RUNX1 corepressor complex with PRMT6 is exchanged with a RUNX1 coactivator complex. Furthermore, the potential cross talk of transcription factors and epigenetic cofactors with histone marks will be discussed.