Furthermore, since ERG is the top upstream regulator of the genes within the AML-enriched blocks (Fig 6A) and is itself downregulated by G9a (Fig 7E), our finding indicates that ERG may act as a part of a regulatory circuit in which its repression by G9a/GLP may lead to a decreased expression of downstream genes positively regulated by ERG and negatively by G9a/GLP-mediated H3K9me2. This evidence concerns the gene EHMT1 and acute myeloid leukemia.