Enhancer methylation defines gradients of cell-type transcription levels. (A)An example of gene-enhancer pair in the RSC1A1 gene region. Gray boxes mark an enhancer methylation site associated with expression of the RSC1A1 gene, and the promoter of this gene. The x-y scatters below the map show methylation versus expression across the cell types for the promoter methylation sites (left), and for the enhancer site (right). The middlescatter shows the methylation of the promoter sites versus methylation of the enhancer across the cell types. (B) Similar to A, but for an enhancer within the first intron of the HSGG2 gene, interacting with HSGG2expression. (C) Models for enhancer control of cell-type expression levels. Upper panel: The traditional model suggesting that enhancers act like cell-type-specific switches of gene transcription, each of them supports expression in a given cell type (or types). Bottom: A refined model suggesting that even a single enhancer site may functions as a dimmer switch, mediating gradients of transcription levels across many cell types as long as the promoter is unmethylated and thus permissive for transcription. RMA, (Robust Multi-chip Average).