{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:25:35Z","timestamp":1790101535584,"version":"4.0.1"},"reference-count":25,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"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":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2018,7,31]]},"abstract":"\n Background:<\/jats:title>\n \n Huntington\u2019s disease is a late onset neurological disorder caused by a trinucleotide CAG repeat expansion mutation in the\n HTT<\/jats:italic>\n gene encoding for the protein huntingtin. Despite considerable ongoing research, the wild-type function of huntingtin is not yet fully understood.\n <\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n \n To improve knowledge of\n HTT<\/jats:italic>\n gene regulation at the transcriptional level and inform future studies aimed at uncovering the\n HTT<\/jats:italic>\n gene\u2019s normal function.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n The\n HTT<\/jats:italic>\n gene region was functionally characterized through an\n in silico<\/jats:italic>\n analysis using publicly available data sets. ChIP-seq data sets and the online STRING database were used to identify putative transcription factor binding sites (TFBSs) and protein-protein interactions within the\n HTT<\/jats:italic>\n promoter region. siRNA-mediated knockdown and ChIP-qPCR of\n STAT1<\/jats:italic>\n , a TF identified from the\n in silico<\/jats:italic>\n analysis, were used to validate the bioinformatics screen.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n 16 regions containing potential regulatory genomic markers were identified. TFBSs for 59 transcription factors (TFs) were detected in one or more of the 16 candidate regions. Using these TFs, 15 clusters of protein-protein interactions were identified using STRING. siRNA-mediated knockdown of\n STAT1<\/jats:italic>\n resulted in an increase in\n HTT<\/jats:italic>\n expression, and ChIP-qPCR detected enrichment of STAT1 binding at one of the predicted regions. These assays confirmed the utility of the bioinformatic analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Putative regulatory regions outside of the immediate\n HTT<\/jats:italic>\n promoter region have been identified with specific protein-protein interactions. Future work will focus on\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n studies to examine the effect of modulating identified TFBSs and altering the levels of specific TFs of interest in regulating\n HTT<\/jats:italic>\n gene expression.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3233\/jhd-170272","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T18:31:21Z","timestamp":1533061881000},"page":"223-237","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Computational Analysis of Transcriptional Regulation Sites at the\n HTT<\/i>\n Gene Locus"],"prefix":"10.1177","volume":"7","author":[{"given":"Rebecca A.G.","family":"De Souza","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kosior","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Mathelier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Be\u010danovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyeth W.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children\u2019s Hospital, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,7,31]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-398"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4014"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0358"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.831000"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12787"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0648-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105136"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-10-r207"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt997"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1315"},{"issue":"1","key":"e_1_3_3_12_2","first-page":"D808","article-title":"STRING v9","volume":"41","author":"Franceschini A","year":"2012","unstructured":"FranceschiniA, SzklarczykD, FrankildS, KuhnM, SimonovicM, RothA, et al.STRING v9. Protein-protein interaction networks with increased coverage and integration. Nucleic Acids Res. 2012;41(D1):D808\u2013D815.","journal-title":"Protein-protein interaction networks with increased coverage and integration. Nucleic Acids Res"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01291-13"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312523111"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90345-3"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw076"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203525"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/currents.hd.5791c897b5c3bebeed93b1d1da0c0648"},{"issue":"60","key":"e_1_3_3_20_2","first-page":"1","article-title":"A common gene expression signature in Huntington\u2019s disease patient brain regions","volume":"7","author":"Neueder A","year":"2014","unstructured":"NeuederA, BatesGP. A common gene expression signature in Huntington\u2019s disease patient brain regions. 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