Model of iHMR behavior at a B cell specifically expressed gene. Shared DHS sites are pre-established in the embryonic stem cell. Hypomethylation at the CpG Island gene promoter (right) and at a CTCF iHMR (left) is constant during development. The enhancer-like iHMR (middle) is fully methylated in H1 ESC. In blood-specified progenitors (HSPCs), it becomes partially demethylated but remains inactive, i.e., lacks H3K4 methylation and RNA transcription. In the B cell state, where the gene is expressed, the promoter HMR expands beyond the core CGI region, and the iHMR becomes fully hypomethylated. The enhancer-like iHMR displays an active enhancer chromatin state (H3K4me1, H3K27ac). It is bound by TBP and RNA Pol II at specific sequence elements (including the TATA box), which initiate eRNA transcription within the iHMR.
