{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:08:48Z","timestamp":1788952128103,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Syst. Biol."],"abstract":"<jats:p>Transcription-factor involvement in drug-adaptive chromatin remodelling is often inferred from motif enrichment in differential ATAC-seq peaks, but such analyses can be distorted by sequence composition, peak length, baseline accessibility and redundant motif models. We reanalysed 105,048 consensus ATAC-seq peaks from an olaparib-adapted Kuramochi ovarian-cancer continuum using HOMER-calibrated AP-1\/bZIP models with coordinate-level de-duplication. At T320, 27,154 peaks gained and 30,050 lost accessibility. AP-1 motif-occurrence density remained higher in gained chromatin under complementary adjustments: an all-peak spline-adjusted Poisson model gave a rate ratio of 1.90 (95% CI 1.80\u20132.01), overlap weighting gave 1.95 (1.82\u20132.11), and 14,046 covariate-matched pairs gave 1.97 (1.90\u20132.05). Following 35,325 fixed motif-positive\/motif-negative peak pairs across the adapted series showed a positive accessibility trend of 0.0363 contrast units per dose doubling (95% CI 0.0195\u20130.0531). Raw paired-end ATAC-seq footprinting provided an orthogonal signal: AP-1 motif intervals scored above same-length motif-free controls selected within the same accessible peaks in every sample, and the AP-1-specific footprint score increased by 0.00509 per dose doubling after replicate adjustment (HC3 95% CI 0.00081\u20130.00937; exact stratified permutation P = 0.00211). In a matched-background genome-wide scan, related AP-1\/bZIP models occupied the nine highest ranks. Within gained chromatin, motif-positive peaks showed greater adjusted overlap with pooled public AP-1 summits (OR 3.82, 95% CI 3.52\u20134.15); after collapsing related files by study, 71 study clusters gave a random-effects OR of 2.68 (2.51\u20132.87), with substantial heterogeneity and a prediction interval of 1.58\u20134.54. Multi-model single-cell and independent bulk-RNA analyses indicated context-dependent downstream AP-1 output, whereas the two valid comparable drug-free CRISPR contrasts were not FDR-significant. Exploratory nearest-TSS mapping of AP-1-rich gained peaks identified 899 protein-coding genes; recurring GO, Reactome and KEGG themes and STRING associations were used only to provide qualitative, hypothesis-generating functional context. Together, the data support a robust association between AP-1-compatible chromatin architecture and olaparib adaptation, while not establishing AP-1 occupancy, necessity or sufficiency in the studied cells.<\/jats:p>","DOI":"10.3389\/fsysb.2026.1859256","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:11:47Z","timestamp":1788948707000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Covariate-adjusted AP-1 motif architecture and footprinting track olaparib-adaptive chromatin remodelling"],"prefix":"10.3389","volume":"6","author":[{"given":"Subhajit","family":"Dutta","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology (IBMZ), Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/s41588-019-0564-y","article-title":"Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer","volume":"52","author":"Akdemir","year":"2020","journal-title":"Nat. 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