DNMT3B and vitamin B deficiency: Although cell culture studies have not supported Alu elements as DNMT3B targets [36,39] in both in vitro and in vivo models, DNMT3b protein levels were down-regulated by B vitamin deficiency (deficiency of folate, B-6, and B-12 together), de novo methylation was suppressed both in vitro and in vivo under conditions of B vitamin deficiency[40], and S-adenosylmethionine levels were markedly decreased in response to lowered B-6 concentrations in culture medium [32] consistent with the direction of association observed here.