{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:38:40Z","timestamp":1772782720102,"version":"3.50.1"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,2,6]]},"abstract":"\n Background<\/jats:title>\n \n The signals that determine atherosclerosis\u2010specific\n DNA<\/jats:styled-content>\n methylation profiles are only partially known. We previously identified a 29\u2010bp\n DNA<\/jats:styled-content>\n motif (differential methylation motif [\n DMM]<\/jats:styled-content>\n ) proximal to CpG islands (\n CGI<\/jats:styled-content>\n s) that undergo demethylation in advanced human atheromas. Those data hinted that the\n DMM<\/jats:styled-content>\n docks modifiers of\n DNA<\/jats:styled-content>\n methylation and transcription.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We sought to functionally characterize the\n DMM<\/jats:styled-content>\n . We showed that the\n DMM<\/jats:styled-content>\n overlaps with the\n RNA<\/jats:styled-content>\n polymerase\n III<\/jats:styled-content>\n \u2013binding B box of\n Alu<\/jats:italic>\n short interspersed nuclear elements and contains a\n DR<\/jats:styled-content>\n 2 nuclear receptor response element. Pointing to a possible functional role for an\n Alu<\/jats:italic>\n DMM<\/jats:styled-content>\n ,\n CGI<\/jats:styled-content>\n s proximal (<100\u00a0bp) to near\u2010intact\n DMM<\/jats:styled-content>\n \u2013harboring\n Alu<\/jats:italic>\n are significantly less methylated relative to\n CGI<\/jats:styled-content>\n s proximal to degenerate\n DMM<\/jats:styled-content>\n \u2013harboring\n Alu<\/jats:italic>\n or to\n DMM<\/jats:styled-content>\n \u2010devoid mammalian\u2010wide interspersed repeat short interspersed nuclear elements in human arteries. As for\n DMM<\/jats:styled-content>\n \u2010binding factors, LXRB (liver X receptor \u03b2) binds the\n DMM<\/jats:styled-content>\n in a\n DR<\/jats:styled-content>\n 2\u2010dependent fashion, and LXR (liver X receptor) agonists induce significant hypermethylation of the bulk of\n Alu<\/jats:italic>\n in\n THP<\/jats:styled-content>\n \u20101 cells. Furthermore, we describe 3 intergenic long noncoding\n RNA<\/jats:styled-content>\n s that harbor a\n DMM<\/jats:styled-content>\n , are under transcriptional control by\n LXR<\/jats:styled-content>\n agonists, and are differentially expressed between normal and atherosclerotic human aortas. Notably,\n CGI<\/jats:styled-content>\n s adjacent to those long noncoding\n RNA<\/jats:styled-content>\n s tend to be hypomethylated in symptomatic relative to stable human atheromas.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Collectively, the data suggest that a\n DMM<\/jats:styled-content>\n is associated with 2 distinct methylation states: relatively low methylation of\n in cis<\/jats:italic>\n CGI<\/jats:styled-content>\n s and\n Alu<\/jats:italic>\n element hypermethylation. Based on the known atheroprotective role of\n LXR<\/jats:styled-content>\n s, we propose that\n LXR<\/jats:styled-content>\n agonist\u2013induced\n Alu<\/jats:italic>\n hypermethylation, a landmark of atherosclerosis, is a compensatory rather than proatherogenic response.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.007686","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T01:10:29Z","timestamp":1517447429000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Liver X Receptor\u2013Binding DNA Motif Associated With Atherosclerosis\u2010Specific DNA Methylation Profiles of\n Alu<\/i>\n Elements and Neighboring CpG Islands"],"prefix":"10.1161","volume":"7","author":[{"given":"Fabiola E.","family":"Trist\u00e1n\u2010Flores","sequence":"first","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Plinio","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melany S.","family":"Ortega\u2010Kermedy","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Cruz\u2010Torres","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Health Sciences, Le\u00f3n Campus, University of Guanajuato, Le\u00f3n, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"de la Rocha","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo A.","family":"Silva\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia","family":"Rodr\u00edguez\u2010R\u00edos","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda","family":"Alvarado\u2010Caudillo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Health Sciences, Le\u00f3n Campus, University of Guanajuato, Le\u00f3n, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Barbosa\u2010Sabanero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Health Sciences, Le\u00f3n Campus, University of Guanajuato, Le\u00f3n, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergi","family":"Sayols","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology gGmbH, Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gertrud","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio","family":"Zaina","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Health Sciences, Le\u00f3n Campus, University of Guanajuato, Le\u00f3n, Gto, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"46","article-title":"Epigenetics and cardiovascular disease","volume":"29","author":"Ordov\u00e1s J","year":"2010","unstructured":"Ordov\u00e1s J, Smith C. 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