{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:06:28Z","timestamp":1784729188189,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,20]]},"group-title":"Genomics","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  UHRF1 is a chromatin-binding protein essential for maintaining DNA methylation and histone modification states, yet its integrated role\n                  <jats:italic>in vivo<\/jats:italic>\n                  remains incompletely understood. To define its function, we generated conditional\n                  <jats:italic>Uhrf1<\/jats:italic>\n                  knockout embryonic stem cells (ESCs) and embryos.\n                  <jats:italic>Uhrf1<\/jats:italic>\n                  \u207b\n                  <jats:sup>\/<\/jats:sup>\n                  \u207b ESCs exhibited near-complete loss of 5mC and 5hmC but maintained pluripotency, whereas Uhrf1-null embryos developed normally until E8.5 and then failed to develop further by E9.5, phenocopying\n                  <jats:italic>Dnmt1<\/jats:italic>\n                  loss. Single-cell multi-omic (ME-seq) profiling of E8.5 embryos revealed impaired lineage stabilization, widespread hypomethylation, and disrupted chromatin architecture.\n                  <jats:italic>Uhrf1<\/jats:italic>\n                  loss was associated with altered CTCF-associated chromatin signal, broad remodeling of chromatin contacts, altered\n                  <jats:italic>cis<\/jats:italic>\n                  -regulatory relationships, and reduced predicted BMP-related ligand\u2013receptor communication, particularly within neural crest populations. These findings identify\n                  <jats:italic>Uhrf1<\/jats:italic>\n                  as a central regulator that tightly couples DNA methylation maintenance to 3D genome organization during gastrulation, thereby, directing early lineage specification and positioning\n                  <jats:italic>Uhrf1<\/jats:italic>\n                  as a pivotal mediator of epigenetic information transfer during early embryogenesis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Uhrf1<\/jats:italic>\n                        knockout ESCs show global loss of 5mC\/5hmC but maintain pluripotency.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>Uhrf1<\/jats:italic>\n                        -null embryos develop normally until E8.5 but die by E9.5 with severe defects.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Single-cell multi-omics revealed disrupted chromatin, transcription, and lineage stability upon knockout.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Loss of Uhrf1 alters CTCF-associated chromatin signal, predicted BMP-related communication, and\n                        <jats:italic>cis<\/jats:italic>\n                        -regulatory relationships.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"738670v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.15.738670","type":"posted-content","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:30:17Z","timestamp":1784590217000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Uhrf1<\/i>\n                  loss disrupts Ctcf-associated chromatin organization during early mouse embryogenesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-571X","authenticated-orcid":false,"given":"Agata","family":"Kurowski","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"The Mount Sinai Center for RNA Biology and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9823-8630","authenticated-orcid":false,"given":"Bohan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"The Mount Sinai Center for RNA Biology and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sargunas","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimisha","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lahouaria","family":"Hadri","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-8285","authenticated-orcid":false,"given":"Martin J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"The Mount Sinai Center for RNA Biology and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, 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