Role of distinct surfaces of the G9a ankyrin repeat domain in histone and DNA methylation during embryonic stem cell self-renewal and differentiation

Background Epigenetic modifications such as histone and DNA methylation are essential for silencing pluripotency genes during embryonic stem cell (ESC) differentiation. G9a is the major histone H3 Lys9 (H3K9) methyltransferase in euchromatin and is required for the de novo DNA methylation of the key regulator of pluripotency Oct3/4 during ESC differentiation. Surprisingly, the catalytic activity of G9a is not required for its role in de novo DNA methylation and the precise molecular mechanisms of G9a in this process are poorly understood. It has been suggested that the G9a ankyrin repeat domain, which can interact with both H3K9me2 and the DNA methyltransferase DNMT3A, could facilitate de novo DNA methylation by bridging the interaction between DNMT3A and H3K9me2-marked chromatin.