{"paper":{"title":"Autonomous Reshaping of Expression Landscapes by DNA Methylation","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","headline":"DNA methylation feedback can reshape gene expression landscapes over time rather than only stabilizing them.","cross_cats":["cond-mat.soft"],"primary_cat":"q-bio.MN","authors_text":"Kaifeng Wang, Ming Han","submitted_at":"2026-05-14T08:34:57Z","abstract_excerpt":"DNA methylation is usually treated as an epigenetic memory mark: transcriptional history is written into regulatory DNA and later stabilizes a chosen cell identity. This picture explains persistence, but it makes memory passive. Here we show that the same promoter-level coupling required for methylation memory can instead turn methylation into an internal control variable for regulatory dynamics. Transcription-factor occupancy protects regulatory DNA from methylation, while methylation shifts later transcription-factor binding thresholds. Under time-scale separation, this reciprocal loop separ"},"claims":{"count":4,"items":[{"kind":"strongest_claim","text":"this feedback does more than preserve a past state: it autonomously reshapes the expression landscape. In a methylation-coupled toggle, the preferred expression state can move continuously through single-well drift, allowing commitment without first entering a multiwell regime.","source":"verdict.strongest_claim","status":"machine_extracted","claim_id":"C1","attestation":"unclaimed"},{"kind":"weakest_assumption","text":"The assumption of clear time-scale separation between fast expression dynamics and slow methylation flow, which permits the decomposition into conditioned fast dynamics and expression-written slow methylation; if methylation rates are comparable to expression timescales, the autonomous reshaping may not emerge.","source":"verdict.weakest_assumption","status":"machine_extracted","claim_id":"C2","attestation":"unclaimed"},{"kind":"one_line_summary","text":"DNA methylation functions as a slow dynamical coordinate that autonomously reshapes expression landscapes in gene regulatory models through reciprocal feedback with transcription factor occupancy.","source":"verdict.one_line_summary","status":"machine_extracted","claim_id":"C3","attestation":"unclaimed"},{"kind":"headline","text":"DNA methylation feedback can reshape gene expression landscapes over time rather than only stabilizing them.","source":"verdict.pith_extraction.headline","status":"machine_extracted","claim_id":"C4","attestation":"unclaimed"}],"snapshot_sha256":"037ef1276cc2f42ac3e8b343e5d56f7c0140075797fc84468be24a7f38815c1b"},"source":{"id":"2605.14562","kind":"arxiv","version":1},"verdict":{"id":"906ef032-b63c-45ba-831d-04945b2a77ac","model_set":{"reader":"grok-4.3"},"created_at":"2026-05-15T00:49:23.052687Z","strongest_claim":"this feedback does more than preserve a past state: it autonomously reshapes the expression landscape. In a methylation-coupled toggle, the preferred expression state can move continuously through single-well drift, allowing commitment without first entering a multiwell regime.","one_line_summary":"DNA methylation functions as a slow dynamical coordinate that autonomously reshapes expression landscapes in gene regulatory models through reciprocal feedback with transcription factor occupancy.","pipeline_version":"pith-pipeline@v0.9.0","weakest_assumption":"The assumption of clear time-scale separation between fast expression dynamics and slow methylation flow, which permits the decomposition into conditioned fast dynamics and expression-written slow methylation; if methylation rates are comparable to expression timescales, the autonomous reshaping may not emerge.","pith_extraction_headline":"DNA methylation feedback can reshape gene expression landscapes over time rather than only stabilizing them."},"references":{"count":36,"sample":[{"doi":"","year":2002,"title":"Bird, Genes & Development16, 6 (2002)","work_id":"abfa28c7-7bfb-4d23-80b0-93cc8e34371c","ref_index":1,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2014,"title":"E. Li and Y. Zhang, Cold Spring Harbor perspectives in biology6, a019133 (2014)","work_id":"0686ad7a-0876-48de-890f-d93222efff1c","ref_index":2,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2005,"title":"S. B. Baylin, Nature clinical practice Oncology2, S4 (2005)","work_id":"4241bbb3-0410-491f-abae-cb179810b404","ref_index":3,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2024,"title":"S. Fan, L. Ma, C. Song, X. Han, B. Zhong, and Y. Lin, Cell Systems15, 808 (2024)","work_id":"16aa6a42-a0f9-496f-baf8-a2fb979041ce","ref_index":4,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":1994,"title":"M. Brandeis, D. Frank, I. Keshet, Z. Siegfried, M. Mendelsohn, A. Nemes, V. Temper, A. Razin, and H. Cedar, Nature371, 435 (1994)","work_id":"0ef2e921-cb1b-4f42-a80d-9ae6ba23f2d3","ref_index":5,"cited_arxiv_id":"","is_internal_anchor":false}],"resolved_work":36,"snapshot_sha256":"b4198e1307ceae0c93b1b8c8433f7f61094c258381365ec23b19c7ca5684b129","internal_anchors":0},"formal_canon":{"evidence_count":2,"snapshot_sha256":"2658fbb33073ff7ba8401abffd2f13005440d2c6488280f766839d66644196b8"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"}