Fig. 1

Illustration of milk microRNA signaling regulating the expression of BIRC5, the gene encoding the anti-apoptotic protein survivin. a. In the absence of milk-derived miRNAs, p53 suppresses survivin expression and attracts DNA methyltransferase 1 (DNMT1) to the BIRC5 promoter, which results in DNA methylation (yellow circles, gene silencing). DNMT1 binding to histone deacetylase 1 (HDAC1) results in histone deacetylation and subsequent chromatin compaction. b. During milk consumption, milk exosomal microRNAs enter the recipient cells and down-regulate the expression of both TP53 and DNMT1 mRNA leading to increased survivin expression. DNMT1 and HDAC1 are removed from the BIRC5 promoter resulting in DNA promoter demethylation and histone acetylation promoting gene expression and opening chromatin structure. Milk-derived p53- and DNMT1 targeting miRNAs thus operate as a switch regulating gene expression