ATAC-seq and MNase-seq Detect Distinct Modes of Chromatin Accessibility [ATAC-seq]

Two widely used approaches for profiling chromatin accessibility are micrococcal nuclease (MNase)-seq and assay for transposase-accessible chromatin (ATAC)-seq. ATAC-seq peaks are often thought to be equivalent to nucleosome-depleted regions (NDRs) that are defined by MNase-seq; however, these two measurements have not been systematically compared.

Here, we performed a side-by-side comparison of ATAC-seq and MNase-seq in budding yeast and found a substantial discrepancy between ATAC-seq peaks and MNase-defined NDRs. This discrepancy is not primarily explained by intrinsic differences between MNase and Tn5 enzymatic activity. Instead, ATAC-seq peaks and NDRs capture distinct chromatin states.