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Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two DS patients with complete T21 and matched euploid donors into two distinct neural stages corresponding to early- and mid-gestational ages.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Using the Illumina Infinium 450K array, we assessed the DNA methylation pattern of known CpG regions and promoters across the genome in trisomic neural iPSC derivatives, and we identified a total of 500 stably and differentially methylated CpGs that were annotated to CpG islands of 151 genes. The genes were enriched within the DNA binding category, uncovering 37 factors of importance for transcriptional regulation and chromatin structure. In particular, we observed regional epigenetic changes of the transcription factor genes <jats:italic>ZNF69<\/jats:italic>, <jats:italic>ZNF700<\/jats:italic> and <jats:italic>ZNF763<\/jats:italic> as well as the <jats:italic>HOXA3<\/jats:italic>, <jats:italic>HOXB3<\/jats:italic> and <jats:italic>HOXD3<\/jats:italic> genes. A similar clustering of differential methylation was found in the CpG islands of the <jats:italic>HIST1<\/jats:italic> genes suggesting effects on chromatin remodeling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The study shows that early established differential methylation in neural iPSC derivatives with T21 are associated with a set of genes relevant for DS brain development, providing a novel framework for further studies on epigenetic changes and transcriptional dysregulation during T21 neurogenesis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-019-0803-1","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T15:22:58Z","timestamp":1578496978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["DNA methylation changes in Down syndrome derived neural iPSCs uncover co-dysregulation of ZNF and HOX3 families of transcription factors"],"prefix":"10.1186","volume":"12","author":[{"given":"Loora","family":"Laan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Klar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sobol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hoeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoureh","family":"Shahsavani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Kele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrin","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zakaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Anner\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Falk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Schuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-0800","authenticated-orcid":false,"given":"Niklas","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"803_CR1","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1002\/bdra.20735","volume":"88","author":"SE Parker","year":"2010","unstructured":"Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, et al. 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