Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs

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dc.contributor.author Tammimies, Kristiina
dc.contributor.author Bieder, Andrea
dc.contributor.author Lauter, Gilbert
dc.contributor.author Sugiaman-Trapman, Debora
dc.contributor.author Torchet, Rachel
dc.contributor.author Hokkanen, Marie-Estelle
dc.contributor.author Burghoorn, Jan
dc.contributor.author Castrén, Eero
dc.contributor.author Kere, Juha
dc.contributor.author Tapia-Paez, Isabel
dc.contributor.author Swoboda, Peter
dc.date.accessioned 2016-10-21T11:22:01Z
dc.date.available 2016-10-21T11:22:01Z
dc.date.issued 2016-10
dc.identifier.citation Tammimies , K , Bieder , A , Lauter , G , Sugiaman-Trapman , D , Torchet , R , Hokkanen , M-E , Burghoorn , J , Castrén , E , Kere , J , Tapia-Paez , I & Swoboda , P 2016 , ' Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs ' , FASEB Journal , vol. 30 , no. 10 , pp. 3578-3587 . https://doi.org/10.1096/fj.201500124RR
dc.identifier.other PURE: 70162895
dc.identifier.other PURE UUID: 1f4df8be-56bc-4497-9530-81450c766422
dc.identifier.other WOS: 000384329800026
dc.identifier.other Scopus: 84990818572
dc.identifier.other ORCID: /0000-0002-1402-2791/work/29002832
dc.identifier.uri http://hdl.handle.net/10138/167990
dc.description.abstract DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof FASEB Journal
dc.rights cc_by_nc
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject reading disorder
dc.subject ciliopathies
dc.subject gene regulation
dc.subject hTERT-RPE1 cell line
dc.subject ciliary proteins
dc.subject NEURONAL MIGRATION
dc.subject DEVELOPMENTAL DYSLEXIA
dc.subject READING-DISABILITY
dc.subject C. ELEGANS
dc.subject CELL-TYPES
dc.subject H1T GENE
dc.subject CILIOGENESIS
dc.subject EXPRESSION
dc.subject VERTEBRATE
dc.subject POPULATION
dc.subject 3112 Neurosciences
dc.title Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs en
dc.type Article
dc.contributor.organization Neuroscience Center
dc.contributor.organization Eero Castren / Principal Investigator
dc.contributor.organization Research Programs Unit
dc.contributor.organization Juha Kere / Principal Investigator
dc.contributor.organization Research Programme for Molecular Neurology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1096/fj.201500124RR
dc.relation.issn 0892-6638
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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