{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:06:32Z","timestamp":1789499192460,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,11]]},"group-title":"Molecular Biology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Chromatin accessibility shapes the ability of transcription factors (TFs) and the transcriptional machinery to engage genomic DNA and therefore plays a central role in gene regulation. 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 perform a side-by-side comparison of ATAC-seq and MNase-seq in budding yeast and find a large discrepancy between ATAC-seq peaks and MNase-defined NDRs. We show that this discrepancy is not primarily due to the intrinsic differences between MNase and Tn5 enzymatic activity. Instead, ATAC-seq peaks and NDRs capture distinct chromatin states. Specifically, ATAC-seq peaks are enriched at dynamic nucleosomes associated with transcriptional co-regulators, including SAGA and SWI\/SNF, whereas ATAC\u2212 NDRs mark more static nucleosome-free regions at promoters. Depletion of SWI\/SNF reduces ATAC-seq signals without affecting most NDRs. Generation of NDRs and ATAC-seq peaks requires distinct TF properties, and native TFs differ in their ability to produce these two types of open chromatin. Finally, we find that the functional distinctions between ATAC-seq peaks and NDRs are widespread across eukaryotic species, including human cells. Together, our results provide new insights into the biological meaning of chromatin accessibility measured by these two assays.<\/jats:p>","DOI":"10.64898\/2026.09.07.749956","type":"posted-content","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:50:25Z","timestamp":1789145425000},"source":"Crossref","is-referenced-by-count":0,"title":["ATAC-seq and MNase-seq Detect Distinct Modes of Chromatin Accessibility"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-4441","authenticated-orcid":false,"given":"Shane","family":"Stoeber","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Godin","sequence":"additional","affiliation":[{"name":"Department 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