{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T13:52:53Z","timestamp":1771681973589,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KI1887\/2\u20101"],"award-info":[{"award-number":["KI1887\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010linked dystonia\u2010parkinsonism is a neurodegenerative movement disorder. The underlying molecular basis has still not been completely elucidated, but likely involves dysregulation of <jats:italic>TAF1<\/jats:italic> expression. In X\u2010linked dystonia\u2010parkinsonism, 3 disease\u2010specific single\u2010nucleotide changes (DSCs) introduce (DSC12) or abolish (DSC2 and DSC3) CpG dinucleotides and consequently sites of putative DNA methylation. Because transcriptional regulation tightly correlates with specific epigenetic marks, we investigated the role of DNA methylation in the pathogenesis of X\u2010linked dystonia\u2010parkinsonism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA methylation at DSC12, DSC3, and DSC2 was quantified by bisulfite pyrosequencing in DNA from peripheral blood leukocytes, fibroblasts, induced pluripotent stem cell\u2013derived cortical neurons and brain tissue from X\u2010linked dystonia\u2010parkinsonism patients and age\u2010 and sex\u2010matched healthy Filipino controls in a prospective study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, X\u2010linked dystonia\u2010parkinsonism patients showed striking differences in DNA methylation at the 3 investigated CpG sites. Using methylation\u2010sensitive luciferase reporter gene assays and immunoprecipitation, we demonstrated (1) that lack of DNA methylation because of DSC2 and DSC3 affects gene promoter activity and (2) that methylation at all 3 investigated CpG sites alters DNA\u2013protein interaction. Interestingly, DSC3 decreased promoter activity per se compared with wild type, and promoter activity further decreased when methylation was present. Moreover, we identified specific binding of proteins to the investigated DSCs that are associated with splicing and RNA and DNA binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified altered DNA methylation in X\u2010linked dystonia\u2010parkinsonism patients as a possible additional mechanism modulating <jats:italic>TAF1<\/jats:italic> expression and putative novel targets for future therapies using DNA methylation\u2010modifying agents. \u00a9 2020 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28239","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T12:28:01Z","timestamp":1601036881000},"page":"2220-2229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>DNA<\/scp> Methylation as a Potential Molecular Mechanism in X\u2010linked Dystonia\u2010Parkinsonism"],"prefix":"10.1002","volume":"35","author":[{"given":"Christin","family":"Krause","sequence":"first","affiliation":[{"name":"Institute for Human Genetics, Division Epigenetics &amp; Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, Ratzeburger Allee 160, 23562  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susen","family":"Schaake","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Gr\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Sievert","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Division Epigenetics &amp; Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles Jourdan","family":"Reyes","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inke R.","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn\u2010Hergen","family":"Laabs","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland Dominic","family":"Jamora","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, College of Medicine \u2014 Philippine General Hospital University of the Philippines  Manila Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond L.","family":"Rosales","sequence":"additional","affiliation":[{"name":"University of Santo Tomas Hospital  Manila Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cid Czarina E.","family":"Diesta","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Movement Disorders Clinic, Makati Medical Center  Makati City Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Pozojevic","sequence":"additional","affiliation":[{"name":"Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, Ratzeburger Allee 160, 23562  L\u00fcbeck Germany"},{"name":"Section for Functional Genetics, Institute for Human Genetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Gemoll","sequence":"additional","affiliation":[{"name":"Section for Translational Surgical Oncology and Biobanking, Department of Surgery University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Westenberger","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Section for Functional Genetics, Institute for Human Genetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Human Genetics University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7887-247X","authenticated-orcid":false,"given":"Henriette","family":"Kirchner","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Division Epigenetics &amp; Metabolism University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center of Brain, Behavior and Metabolism (CBBM), University of L\u00fcbeck, Ratzeburger Allee 160, 23562  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2010.526728"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.292"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1831949100"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/512129"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds499"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2159-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.022590"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.011"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27441"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712526114"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25488"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.1.3.3327"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1049"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.772403"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08514"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25369"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.56"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708044114"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(00)00393-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087505"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335770"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.4.1430"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.069"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.101907.109"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.143503.112"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10442"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.110"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.038"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05587-11"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.11.019"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16462"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041361"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.93"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28239","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.28239","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.28239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:53:38Z","timestamp":1760950418000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.28239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,10]]},"references-count":33,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/mds.28239"],"URL":"https:\/\/doi.org\/10.1002\/mds.28239","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,10]]},"assertion":[{"value":"2019-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}