{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:49:14Z","timestamp":1793915354332,"version":"4.8.0"},"posted":{"date-parts":[[2026,1,29]]},"group-title":"Molecular Biology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Transcription factors (TFs) bind to enhancers and recruit H3K4me1 methyltransferase KMT2D, chromatin remodeler BAF, and H3K27 acetyltransferase p300 to activate transcription. However, the role of chromatin modifiers in regulating\n                  <jats:italic>de novo<\/jats:italic>\n                  binding of TFs on enhancers remains unclear. Using a robust nuclear translocation system, we show that the muscle lineage-determining TF MyoD binds to chromatin pervasively within one hour, with half of induced MyoD binding sites co-occupied by KMT2D, BAF, and p300. On the majority of these MyoD\n                  <jats:sup>+<\/jats:sup>\n                  enhancers, acute depletion of KMT2D or short-term inhibition of BAF or p300 enzymatic activity markedly reduces\n                  <jats:italic>de novo<\/jats:italic>\n                  binding of MyoD as well as that of KMT2D, BAF, and p300. On enhancers with intact MyoD binding despite these perturbations, we observe a cooperative recruitment among chromatin modifiers. Similar interdependent relationships are observed between the signal-dependent TF Glucocorticoid Receptor and KMT2D, BAF, and p300. Together, our findings show that chromatin modifiers are not only downstream effectors but also required for\n                  <jats:italic>de novo<\/jats:italic>\n                  binding of TFs on enhancers, refining a model of enhancer establishment as a process governed by functional cooperation rather than a strict hierarchy.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Bullet points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        Acute KMT2D depletion disrupts\n                        <jats:italic>de novo<\/jats:italic>\n                        binding of MyoD, BAF, and p300 on enhancers.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        BAF and p300 enzymatic activities are required for\n                        <jats:italic>de novo<\/jats:italic>\n                        binding of MyoD, BAF, KMT2D, and p300 on enhancers.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Cooperative binding of KMT2D, BAF, and p300 on MyoD\n                        <jats:sup>+<\/jats:sup>\n                        enhancers.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>GR displays interdependencies with chromatin modifiers KMT2D, BAF, and p300 on enhancers.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.29.702555","type":"posted-content","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:40:12Z","timestamp":1769762412000},"source":"Crossref","is-referenced-by-count":2,"title":["Chromatin modifiers KMT2D, BAF, and p300 are required for\n                  <i>de novo<\/i>\n                  binding of transcription factors on enhancers"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-915X","authenticated-orcid":false,"given":"Hieu T.","family":"Van","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-7233","authenticated-orcid":false,"given":"Young-Kwon","family":"Park","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Transgenic Core, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamima","family":"Islam","sequence":"additional","affiliation":[{"name":"Genome Technology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-5631","authenticated-orcid":false,"given":"Stefania","family":"Dell\u2019Orso","sequence":"additional","affiliation":[{"name":"Genome Technology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-9091","authenticated-orcid":false,"given":"Weiqun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Physics and Department of Anatomy and Cell Biology, The George Washington University, Washington, DC 20052"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-3675","authenticated-orcid":false,"given":"Vittorio","family":"Sartorelli","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Stem Cells and Gene Regulation, NIAMS, NIH, Bethesda, MD 208292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-7016","authenticated-orcid":false,"given":"Ji-Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7442-5138","authenticated-orcid":false,"given":"Kai","family":"Ge","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 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