FIG. 10.

Proposed model of gene expression modulation by changes in H4 arginine 3 methylation. PRMT1 and PAD4 regulate arginine 3 methylation. The naive state is characterized by lack of H4 arginine methylation on the enhancer region. Priming results in increased H4 R3 methylation, while retinoid treatment leads to decreased H4R3 methylation and to the indicated changes in lysine acetylation. Preacetylation of histone tails prior to priming by TSA is likely to reduce the affinity of histone tails toward PRMT1 and, by this, prevents the enhanced retinoid responsiveness caused by priming. The activation of PAD4 after priming by calcium ionophore treatment leads to the removal of the methyl mark from H4R3 and abolition of the enhanced retinoid responsiveness caused by priming.