{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T11:55:25Z","timestamp":1782561325598,"version":"3.54.5"},"reference-count":64,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>\n                    DNA methylation epigenetically regulates gene expression. This study is aimed to investigate genome-wide DNA methylations involved in the regulation of palatal fusion in the all-\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    retinoic acid-induced mouse cleft palate model. There were 4,718,556 differentially CCGG methylated sites and 367,504 CCWGG methylated sites for 1497 genes between case and control embryonic mouse palatal tissues. The enhancers (\n                    <jats:italic toggle=\"yes\">HDAC4<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">SMAD3<\/jats:italic>\n                    ) and promoter (\n                    <jats:italic toggle=\"yes\">MID1<\/jats:italic>\n                    ) of these three genes had\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -acting element methylation.\n                    <jats:italic toggle=\"yes\">HDAC4<\/jats:italic>\n                    is localized within the CCWGG, while\n                    <jats:italic toggle=\"yes\">MID1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">SMAD3<\/jats:italic>\n                    are localized within the CCGG of the gene intron. The methylation-specific polymerase chain reaction data confirmed the MethylRAD-seq results, while the quantitative reverse transcriptase-polymerase chain reaction result showed that changes in gene expression inversely were associated with the\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -acting element methylation of the gene during retinoic acid-induced palatal fusion. The GO and KEGG data showed that these three genes could regulate cell proliferation, skeletal muscle fiber development, and development-related gene signaling or activity. The\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -acting element methylation of\n                    <jats:italic toggle=\"yes\">HDAC4<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SMAD3<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">MID1<\/jats:italic>\n                    may play a regulatory role during palatal fusion. Further research is needed to verify these novel epigenetic biomarkers for cleft palate.\n                  <\/jats:p>","DOI":"10.1089\/dna.2018.4369","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T12:12:55Z","timestamp":1538482375000},"page":"993-1002","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Genome-Wide DNA Methylation Profile of Gene\n                    <i>cis<\/i>\n                    -Acting Element Methylations in All-\n                    <i>trans<\/i>\n                    Retinoic Acid-Induced Mouse Cleft Palate"],"prefix":"10.1177","volume":"37","author":[{"given":"Xuan","family":"Shu","sequence":"first","affiliation":[{"name":"The Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenyou","family":"Shu","sequence":"additional","affiliation":[{"name":"The Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Zhai","sequence":"additional","affiliation":[{"name":"The Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Ouyang","sequence":"additional","affiliation":[{"name":"The Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,12,8]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2011.00425.x"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02721-0"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3088-6"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.07.011"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.19.2325"},{"key":"e_1_3_3_8_1","first-page":"469","article-title":"Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate","volume":"35","author":"Beaty T.","year":"2011","unstructured":"Beaty T., , Ruczinski I., , Murray J., , Marazita M., , Munger R., , Hetmanski J., et al. 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