{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:31:26Z","timestamp":1763389886516,"version":"3.41.0"},"posted":{"date-parts":[[2024,7,3]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,5]]},"abstract":"<title>Abstract<\/title>\n        <p>Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. In past work, we discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2\/G9a) inhibitors were capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document unsilencing of the imprinted Snrpn\/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a new and distinct noncoding RNA preferentially transcribed from upstream of the PWS-IC interacts with EHMT2 and forms a heterochromatin complex to silence gene expression of SNRPN in CIS on maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide novel mechanistic insights and support a new model for imprinting maintenance of the PWS imprinted\ndomain.<\/p>","DOI":"10.21203\/rs.3.rs-4530649\/v1","type":"posted-content","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T04:28:28Z","timestamp":1719980908000},"source":"Crossref","is-referenced-by-count":1,"title":["Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6188-8806","authenticated-orcid":false,"given":"Yong-hui","family":"Jiang","sequence":"first","affiliation":[{"name":"Yale University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Eun","family":"Wang","sequence":"additional","affiliation":[{"name":"Yale Unviersity"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Yale University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaechul","family":"Lim","sequence":"additional","affiliation":[{"name":"Seoul National University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Ae","family":"Jang","sequence":"additional","affiliation":[{"name":"Samsung Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Forrest","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuna","family":"Kim","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meaghan","family":"Donahue","sequence":"additional","affiliation":[{"name":"Yale University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Nan","family":"Qiao","sequence":"additional","affiliation":[{"name":"Yale University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-3862","authenticated-orcid":false,"given":"Jian","family":"Jin","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-4064","authenticated-orcid":false,"given":"Siyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Yale University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4530649\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4530649\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T07:09:45Z","timestamp":1751612985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4530649\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-4530649\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41467-025-61156-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,7,3]]},"subtype":"preprint"}}