{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:17:30Z","timestamp":1785187050964,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP25462567"],"award-info":[{"award-number":["JP25462567"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP20K09644"],"award-info":[{"award-number":["JP20K09644"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP17K11238"],"award-info":[{"award-number":["JP17K11238"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["R01HD094937"],"award-info":[{"award-number":["R01HD094937"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["JP25462567"],"award-info":[{"award-number":["JP25462567"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["JP20K09644"],"award-info":[{"award-number":["JP20K09644"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["JP17K11238"],"award-info":[{"award-number":["JP17K11238"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD094937"],"award-info":[{"award-number":["R01HD094937"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cell fusion in the placenta is tightly regulated. Suppressyn is a human placental endogenous retroviral protein that inhibits the profusogenic activities of another well-described endogenous retroviral protein, syncytin-1. In this study, we aimed to elucidate the mechanisms underlying suppressyn\u2019s placenta-specific expression. We identified the promoter region and a novel enhancer region for the gene encoding suppressyn, ERVH48-1, and examined their regulation via DNA methylation and their responses to changes in the oxygen concentration. Like other endogenous retroviral genes, the ERVH48-1 promoter sequence is found within a characteristic retroviral 5\u2032 LTR sequence. The novel enhancer sequence we describe here is downstream of this LTR sequence (designated EIEs: ERV internal enhancer sequence) and governs placental expression. The placenta-specific expression of ERVH48-1 is tightly controlled by DNA methylation and further regulated by oxygen concentration-dependent, hypoxia-induced transcription factors (HIF1\u03b1 and HIF2\u03b1). Our findings highlight the involvement of (1) tissue specificity through DNA methylation, (2) expression specificity through placenta-specific enhancer regions, and (3) the regulation of suppressyn expression in differing oxygen conditions by HIF1\u03b1 and HIF2\u03b1. We suggest that these regulatory mechanisms are central to normal and abnormal placental development, including the development of disorders of pregnancy involving altered oxygenation, such as preeclampsia, pregnancy-induced hypertension, and fetal growth restriction.<\/jats:p>","DOI":"10.3390\/biom13111627","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:23:39Z","timestamp":1699356219000},"page":"1627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Controlling Trophoblast Cell Fusion in the Human Placenta\u2014Transcriptional Regulation of Suppressyn, an Endogenous Inhibitor of Syncytin-1"],"prefix":"10.3390","volume":"13","author":[{"given":"Jun","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny J.","family":"Schust","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Duke University, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Jinno","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of the Ryukyus, Okinawa 903-0215, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6542-3408","authenticated-orcid":false,"given":"Yoshiki","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1146\/annurev.genet.42.110807.091501","article-title":"Effects of Retroviruses on Host Genome Function","volume":"42","author":"Jern","year":"2008","journal-title":"Annu. 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