I have DNase-seq data for mouse embryonic stem cells (mESCs) and mouse embryonic fibroblast cells (MEFs). By their nature stem cells have a more globally accessible chromatin structure compared to somatic cells. I created a plot comparing the TSS coverage (normalised to RPM) of stem-cell specific genes and found that MEFs had much higher coverage. Is it possible that because their is less accessible chromatin in the MEFs I am seeing a higher coverage simply because it is a less complex library? Are there any normalisation methods which take into account the accessibility of the genome?