Two epigenetic pathways converge to control NFE2 expression in the MPNs. (A) In healthy hematopoietic cells, NFE2 expression is maintained at a low level by HP1α binding to unphosphorylated H3Y41 and by the presence of dimethylated H3K9. (B) In MPN cells, NFE2 expression is upregulated by both a reduction in HP1α binding, which is associated with increased phosphorylation of H3Y41 by JAK2^V617F and by demethylation of H3K9. The figure has been adapted from Figure 6 in the article by Peeken et al that begins on page 2065.