BACKGROUND: DNA methylation, histone modifications and nucleosome occupancy act 
in concert for regulation of gene expression patterns in mammalian cells. 
Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in 
establishment of DNA methylation at embryonic gene targets in ES cells through 
recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar 
role in maintenance of DNA methylation in somatic cells is still unclear.
RESULTS: Here we show that G9a is not essential for maintenance of DNA 
methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA 
methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to 
nucleosomes containing methylated DNA even in the absence of G9a, ensuring 
faithful propagation of methylated states in cooperation with DNMT1 through 
somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B 
and DNA methylation-independent manner. However, G9a knockdown synergizes with 
pharmacologic inhibition of DNMTs resulting in increased hypomethylation and 
inhibition of cell proliferation.
CONCLUSIONS: Taken together, these data suggest that G9a is not involved in 
maintenance of DNA methylation in somatic cells but might play a role in 
re-initiation of de novo methylation after treatment with hypomethylating drugs, 
thus serving as a potential target for combinatorial treatments strategies 
involving DNMTs inhibitors.