Transcription factor occupancy is linked to DNA methylation turnover at active regulatory regions [MeDIP-Seq]

Genome wide analysis revealed that distal regulatory elements form Low Methylated Regions (LMRs). Even though transcription factor binding is required for LMR formation, we show for the test case CTCF that actual occupancy does not distinguish DNA methylation states. However, in line with a dynamic model of binding and DNA methylation turnover, we find that the product of active demethylation, 5-hydroxymethylcytosine (5hmC), is enriched at LMRs. 5hmC is present at active regulatory regions in stem and somatic cells and as a result a substantial fraction of changes in 5hmC occurs at LMRs. This suggests that transcription factor binding mediates active turnover of DNA methylation as an integral part of reprogramming of regulatory regions. Overall design: hMeDIP sequencing in mouse embryonic stem cells (ES) and derived neuronal progenitors (NP).