Single-molecule simultaneous profiling of DNA methylation and DNA-protein interactions with Nanopore-DamID
Cheetham, S. W.; Jafrani, Y. M. A.; Andersen, S. B.; Jansz, N.; Ewing, A. D.; Faulkner, G. J.
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We present Nanopore-DamID, a method to simultaneously detect cytosine methylation and DNA-protein interactions from single molecules, via selective sequencing of adenine-labelled DNA. Assaying LaminB1 and CTCF binding with Nanopore-DamID, we identify escape from LAD-associated repression of hypomethylated promoters amidst generalised hypermethylation of LaminB1-associated regulatory elements. We detect novel CTCF binding sites in highly repetitive regions, and allele-specific CTCF binding to imprinted genes and the active X chromosome. Nanopore-DamID highlights the importance of DNA methylation to transcription factor activity.
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