Proteins
and enzymes in the cell nucleus require physical access
to their DNA target sites in order to perform genomic tasks such as
gene activation and transcription. Hence, chromatin accessibility
is a central regulator of gene expression, and its genomic profile
holds essential information on the cell type and state. We utilized
theE. coliDam methyltransferase in
combination with a fluorescent cofactor analogue to generate fluorescent
tags in accessible DNA regions within the cell nucleus. The accessible
portions of the genome are then detected by single-molecule optical
genome mapping in nanochannel arrays. This method allowed us to characterize
long-range structural variations and their associated chromatin structure.
We show the ability to create whole-genome, allele-specific chromatin
accessibility maps composed of long DNA molecules extended in silicon
nanochannels.