A crosstalk between histone methylation and DNA methylation in gene silencing

Anti Damayanti Hamdani
41917325

Histone and DNA methylation are heritable epigenetic modification for programming gene expression profiles. While DNA methylation leads to stable and long-term repression, histone methylation plays a role in readily reversible gene silencing. Though both mechanisms are carried out by different set of chemical reactions, they are actually dependent on one another in directing gene repression patterns. Histone methylation can help to establish DNA methylation patterns and pre-existing DNA methylation may guide the placement of histone modification. This relationship might be accomplished by physical interaction between DNA methyltransferase and histone methyltransferase. The human β-globin locus is used as a model to reveal the crosstalk between arginine methylation of histones and DNA methylation to repress gene expression. Firstly, the protein arginine methyltransferase PRMT5 is symetrically dimethylating histone H4 arginine 3 (H4R3me2s). The repressed histone then serves as an epigenetic mark for direct binding with DNA methyltransferase DNMT3A to subsequently recruit DNA methylation and induce gene silencing. Notably, the knockdown of PRMT5 by short hairpin RNA (shRNA) leads to globin gene activation because the DNMT3A loss the target marks for binding. Thus, in regulating gene repression, DNMT3A provides a direct link between histone and DNA methylation by interpreting repressive marks on histone and inducing DNA methylation.