{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:54Z","timestamp":1792786194733,"version":"4.5.0"},"reference-count":0,"publisher":"Cold Spring Harbor Laboratory","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-165992"],"award-info":[{"award-number":["PJT-165992"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-154297"],"award-info":[{"award-number":["FDN-154297"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["195914"],"award-info":[{"award-number":["195914"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2024-04175"],"award-info":[{"award-number":["RGPIN-2024-04175"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Digital Research Alliance of Canada","award":["zmv-495 553"],"award-info":[{"award-number":["zmv-495 553"]}],"id":[{"id":"https:\/\/ror.org\/010r6td27","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005391","name":"ARC Fondation","doi-asserted-by":"publisher","award":["ARCPJA2023080006958"],"award-info":[{"award-number":["ARCPJA2023080006958"]}],"id":[{"id":"10.13039\/100005391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["MND202310017917"],"award-info":[{"award-number":["MND202310017917"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-22-CE12-0016"],"award-info":[{"award-number":["ANR-22-CE12-0016"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-23-CE12 CORGI"],"award-info":[{"award-number":["ANR-23-CE12 CORGI"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["26ek0109879"],"award-info":[{"award-number":["26ek0109879"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development of Japan","doi-asserted-by":"publisher","award":["2026B-1"],"award-info":[{"award-number":["2026B-1"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"accepted":{"date-parts":[[2026,8,19]]},"abstract":"<jats:p>\n                    KLF14 acts as a master regulator of gene expression in adipose tissue and variants at the human\n                    <jats:italic>KLF14<\/jats:italic>\n                    gene show reproducible association with type 2 diabetes and metabolic syndrome. Risk alleles are only pathological when maternally inherited, consistent with the observation that\n                    <jats:italic>KLF14\/Klf14<\/jats:italic>\n                    is a maternally expressed imprinted gene in human and mouse. However, how genomic imprinting is regulated at this important locus is currently unknown. In both species,\n                    <jats:italic>KLF14\/Klf14<\/jats:italic>\n                    is located \u223c200 kb away from the paternally expressed imprinted gene\n                    <jats:italic>MEST\/Mest<\/jats:italic>\n                    , regulated by a maternal gametic differentially methylated region (gDMR) at its promoter. Although the\n                    <jats:italic>Klf14<\/jats:italic>\n                    promoter is unmethylated in most tissues, maternally inherited DNA methylation marks are paradoxically required for\n                    <jats:italic>Klf14<\/jats:italic>\n                    expression. Here, we show that\n                    <jats:italic>Mest<\/jats:italic>\n                    and\n                    <jats:italic>Klf14<\/jats:italic>\n                    reside within the same topologically associating domain (TAD) in embryonic stem cells (ESCs), defined by biallelic CTCF binding at the boundaries. Using allele-specific 4C-seq, we show that CTCF binding to the unmethylated\n                    <jats:italic>Mest<\/jats:italic>\n                    gDMR generates a paternal allele-specific sub-TAD encompassing\n                    <jats:italic>Klf14<\/jats:italic>\n                    . CRISPR\u2013Cas9 deletions of the paternal\n                    <jats:italic>Mest<\/jats:italic>\n                    promoter region in ESCs and in vivo in mutant mice result in loss of\n                    <jats:italic>Mest<\/jats:italic>\n                    expression and acquisition of biallelic expression at\n                    <jats:italic>Klf14<\/jats:italic>\n                    . By analyzing epigenetic marks and chromatin looping in\n                    <jats:italic>Klf14<\/jats:italic>\n                    -expressing pituitary cells, we identify a putative enhancer element shared by\n                    <jats:italic>Mest<\/jats:italic>\n                    and\n                    <jats:italic>Klf14<\/jats:italic>\n                    , providing a mechanistic model for the regulation of\n                    <jats:italic>Klf14<\/jats:italic>\n                    imprinting. This work defines a new role for the\n                    <jats:italic>Mest<\/jats:italic>\n                    maternally methylated gDMR, revealing that it exerts long-range effects via allele-specific modulation of TAD structures and acts as an imprinting control region in the regulation of\n                    <jats:italic>Klf14<\/jats:italic>\n                    imprinting.\n                  <\/jats:p>","DOI":"10.1101\/gad.353948.126","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:15:12Z","timestamp":1790010912000},"source":"Crossref","is-referenced-by-count":0,"title":["Genomic imprinting of the metabolic regulator gene\n                    <i>Klf14<\/i>\n                    is regulated by a paternal sub-TAD anchored at\n                    <i>Mest<\/i>"],"prefix":"10.1101","author":[{"given":"Amanda","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2013Fetal Biology, National Center for Child Health and Development, Tokyo 157-8535, Japan;"},{"name":"Department of Advanced Pediatric Medicine, Tohoku University School of Medicine, Miyagi 980-8575, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Bogutz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-7892","authenticated-orcid":false,"given":"Benoit","family":"Moindrot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Commissariat \u00e0 l'\u00c9nergie Atomique et aux \u00c9nergies Alternatives, Centre National de la Recherche Scientifique (CNRS), Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette 91198, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gomez","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier (IGMM), University of Montpellier, CNRS, Montpellier F-34293, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1979-767X","authenticated-orcid":false,"given":"Juliette","family":"Harris","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Institut de Recherches Cliniques de Montr\u00e9al (IRCM), Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Marcil","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Institut de Recherches Cliniques de Montr\u00e9al (IRCM), Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0327-9708","authenticated-orcid":false,"given":"Frank","family":"Court","sequence":"additional","affiliation":[{"name":"Genetics, Reproduction and Development Institute (iGReD), CNRS, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Clermont Auvergne, Clermont-Ferrand 63000, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Shindo","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources, National Center for Child Health and Development, Tokyo 157-8535, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-8764","authenticated-orcid":false,"given":"Philippe","family":"Arnaud","sequence":"additional","affiliation":[{"name":"Genetics, Reproduction and Development Institute (iGReD), CNRS, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Clermont Auvergne, Clermont-Ferrand 63000, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-5691","authenticated-orcid":false,"given":"Jacques","family":"Drouin","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Institut de Recherches Cliniques de Montr\u00e9al (IRCM), Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-1551","authenticated-orcid":false,"given":"Thierry","family":"Forn\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier (IGMM), University of Montpellier, CNRS, Montpellier F-34293, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-7002","authenticated-orcid":false,"given":"Daan","family":"Noordermeer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Commissariat \u00e0 l'\u00c9nergie Atomique et aux \u00c9nergies Alternatives, Centre National de la Recherche Scientifique (CNRS), Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette 91198, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Systems Developmental Biology, National Center for Child Health and Development, Tokyo 157-8535, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2927-0963","authenticated-orcid":false,"given":"Kazuhiko","family":"Nakabayashi","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2013Fetal Biology, National Center for Child Health and Development, Tokyo 157-8535, Japan;"},{"name":"Integrated Center for Women's Health (ICWH), National Center for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-9480","authenticated-orcid":false,"given":"Louis","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,9,21]]},"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.353948.126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:15:13Z","timestamp":1790010913000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.353948.126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":0,"alternative-id":["10.1101\/gad.353948.126"],"URL":"https:\/\/doi.org\/10.1101\/gad.353948.126","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}