New understanding of how histone and DNA methylation communicate

In the May 15th issue of G&D, Dr. Michael Carey (UCLA's Jonsson Comprehensive Cancer Center) and colleagues lend new insight into the mechanism of epigenetic silencing of euchromatic genes.

Dr. Carey emphasizes that "The study provides a new direction to understand how histone and DNA methylation, two phenomena that play a significant role in stem cell differentiation and cancer, can communicate with each other to turn genes off. "

Although both histone and DNA methylation have long been recognized as hallmarks of euchromatic gene silencing, how these two processes cooperate to induce silencing has remained unresolved. In their upcoming paper, Dr. Carey and colleagues detail that mammalian HP1 proteins facilitate this cooperation.

They found that HP1 proteins, which bind to methylated histones, also interact with the DNA methyltransferase, DNMT1, to stimulate its DNA methylation activity. DNMT1, in turn, reinforced HP1 binding to methylated histones. Finally, the researchers showed that DNMT1-stimulated HP1 binding is required for gene silencing.