{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:19:03Z","timestamp":1786551543217,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2B3005113"],"award-info":[{"award-number":["2018R1A2B3005113"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2024418"],"award-info":[{"award-number":["NRF-2018R1A5A2024418"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anoctamin1 (ANO1), a calcium activated chloride channel, is known to play a critical role in salivary secretion. In the salivary gland, ANO1 is expressed exclusively in the acinar cells, with no expression in the ductal cells. However, the mechanisms that determine this distinctive cell type-dependent expression pattern of ANO1 remain unknown. In this study, we discovered that the cell-dependent expression of ANO1 during salivary gland organogenesis is regulated by DNA methylation of ANO1 CpG islands. ANO1 CpG islands in e12 embryonic submandibular glands (eSMG) are highly methylated, but those in e14 eSMG or adult SMG are significantly unmethylated. The differential expression pattern of ANO1 in duct and acini is defined at e14. Artificial demethylation by treatment with the demethylating agent 5-aza-2\u2019-deoxycytidine (5-Aza-CdR), induced the expression of ANO1 in both the ductal cell line Human Submandibular Gland (HSG) and in the duct cells of adult mouse SMG. During the trans-differentiation in Matrigel of duct-origin HSG cells into acinar-like phenotype, significant demethylation of ANO1 CpG islands is observed. This may be due to the reduced expression of DNA methyltransferase (DNMT) 3a and 3b. These results suggest that the differential expression of ANO1 in salivary glands during organogenesis and differentiation is mainly regulated by epigenetic demethylation of the ANO1 gene.<\/jats:p>","DOI":"10.3390\/ijms20246298","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T11:27:22Z","timestamp":1576236442000},"page":"6298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Epigenetic Modification as a Regulatory Mechanism for Spatiotemporal Dynamics of ANO1 Expression in Salivary Glands"],"prefix":"10.3390","volume":"20","author":[{"given":"Yonghwan","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 110-749, Korea"},{"name":"Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 110-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Namkoong","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 110-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woojin","family":"An","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-545X","authenticated-orcid":false,"given":"Jong-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul 110-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D","family":"Brown","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-1270","authenticated-orcid":false,"given":"Kyungpyo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul 110-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1074\/jbc.RA118.002378","article-title":"The apical anion exchanger slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells","volume":"293","author":"Mukaibo","year":"2018","journal-title":"J. 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