{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:49:17Z","timestamp":1781279357908,"version":"3.54.1"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"44","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD094373"],"award-info":[{"award-number":["R01 HD094373"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD076450"],"award-info":[{"award-number":["R01HD076450"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:p>\n                    Uterine leiomyomas (UL) are benign tumors that arise in the myometrial layer of the uterus. The standard treatment option for UL is hysterectomy, although hormonal therapies, such as selective progesterone receptor modulators, are often used as temporary treatment options to reduce symptoms or to slow the growth of tumors. However, since the pathogenesis of UL is poorly understood and most hormonal therapies are not based on UL-specific, divergent hormone signaling pathways, hallmarks that predict long-term efficacy and safety of pharmacotherapies remain largely undefined. In a previous study, we reported that aberrant expression of repressor element 1 silencing transcription factor\/neuron-restrictive silencing factor (REST\/NRSF) target genes activate UL growth due to the near ubiquitous loss of REST. Here, we show that ablation of the\n                    <jats:italic>Rest<\/jats:italic>\n                    gene in mouse uterus leads to UL phenotype and gene-expression patterns analogous to UL, including altered estrogen and progesterone signaling pathways. We demonstrate that many of the genes dysregulated in UL harbor\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory elements bound by REST and progesterone receptor (PGR) adjacent to each other. Crucially, we identify an interaction between REST and PGR in healthy myometrium and present a putative mechanism for the dysregulation of progesterone-responsive genes in UL ensuing in the loss of REST. Using three\n                    <jats:italic>Rest<\/jats:italic>\n                    conditional knockout mouse lines, we provide a comprehensive picture of the impact loss of REST has in UL pathogenesis and in altering the response of UL to steroid hormones.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2205524119","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T13:56:17Z","timestamp":1666706177000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Loss of the repressor REST affects progesterone receptor function and promotes uterine leiomyoma pathogenesis"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-8778","authenticated-orcid":false,"given":"Ashley S.","family":"Cloud","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faezeh","family":"Koohestani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"McWilliams","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-5818","authenticated-orcid":false,"given":"Sornakala","family":"Ganeshkumar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2097-135X","authenticated-orcid":false,"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2349-1880","authenticated-orcid":false,"given":"Warren B.","family":"Nothnick","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Institute for Reproduction and Perinatal Research, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vargheese M.","family":"Chennathukuzhi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160"},{"name":"Institute for Reproduction and Perinatal Research, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 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