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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http://hdl.handle.net/10138/167990

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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

Julkaisun nimi: Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs
Tekijä: Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Paez, Isabel; Swoboda, Peter
Tekijän organisaatio: Neuroscience Center
Eero Castren / Principal Investigator
Research Programs Unit
Juha Kere / Principal Investigator
Research Programme for Molecular Neurology
Päiväys: 2016-10
Kieli: eng
Sivumäärä: 10
Kuuluu julkaisusarjaan: FASEB Journal
ISSN: 0892-6638
DOI-tunniste: https://doi.org/10.1096/fj.201500124RR
URI: http://hdl.handle.net/10138/167990
Tiivistelmä: 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.
Avainsanat: reading disorder
ciliopathies
gene regulation
hTERT-RPE1 cell line
ciliary proteins
NEURONAL MIGRATION
DEVELOPMENTAL DYSLEXIA
READING-DISABILITY
C. ELEGANS
CELL-TYPES
H1T GENE
CILIOGENESIS
EXPRESSION
VERTEBRATE
POPULATION
3112 Neurosciences
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by_nc
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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