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

Autor: Isabel Tapia-Páez, Eero Castrén, Andrea Bieder, Kristiina Tammimies, Debora Sugiaman-Trapman, Gilbert Lauter, Peter Swoboda, Rachel Torchet, Marie-Estelle Hokkanen, Juha Kere, Jan Burghoorn
Přispěvatelé: Neuroscience Center, Eero Castren / Principal Investigator, Research Programs Unit, Juha Kere / Principal Investigator, Research Programme for Molecular Neurology, Karolinska Institutet [Stockholm], University of Helsinki, This study was supported by the Swedish Brain Foundation (Hjärnfonden ), the Swedish Research Council, the TorstenSöderberg, Ahlén, Lars Hiertas Minne, and Sigrid Jusélius Foundations, the Swedish Foundation for Strategic Research, the Karolinska Institutet (KI) Strategic Neuroscience Program, and the Academy of Finland. This study was performed, in part, at the Live Cell Imaging Unit/Nikon Center of Excellence at the KI Department of Biosciences and Nutrition, which is supported by grants from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the KI Center for Innovative Medicine, and the Jonasson donation to the School of Technology and Health, Royal Institute of Technology.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
C. ELEGANS
Candidate gene
H1T GENE
MESH: Cytoskeletal Proteins
[SDV]Life Sciences [q-bio]
ciliary proteins
Biochemistry
READING-DISABILITY
Dyslexia
0302 clinical medicine
Genes
Reporter
MESH: Animals
MESH: Nerve Tissue Proteins
Promoter Regions
Genetic
[SDV.BDD]Life Sciences [q-bio]/Development Biology
POPULATION
Cells
Cultured
Genetics
Regulation of gene expression
Cilium
Nuclear Proteins
MESH: Regulatory Factor X Transcription Factors
Cell biology
NEURONAL MIGRATION
Microtubule-Associated Proteins
MESH: Cells
Cultured
Biotechnology
MESH: Dyslexia
EXPRESSION
Nerve Tissue Proteins
Regulatory Factor X Transcription Factors
Biology
03 medical and health sciences
MESH: Cilia
MESH: Caenorhabditis elegans
Ciliogenesis
MESH: Promoter Regions
Genetic
Animals
Humans
Cilia
CELL-TYPES
Caenorhabditis elegans
Molecular Biology
Gene
Transcription factor
CILIOGENESIS
reading disorder
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
Binding Sites
Research
MESH: Genes
Reporter
3112 Neurosciences
MESH: Microtubule-Associated Proteins
Cytoskeletal Proteins
030104 developmental biology
MESH: Binding Sites
RFX1
DEVELOPMENTAL DYSLEXIA
ciliopathies
hTERT-RPE1 cell line
RFX3
VERTEBRATE
gene regulation
MESH: Nuclear Proteins
030217 neurology & neurosurgery
Zdroj: The FASEB Journal
FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2016, 30 (10), pp.3578-3587. ⟨10.1096/fj.201500124RR⟩
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201500124RR⟩
Popis: International audience; 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.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs.
Databáze: OpenAIRE
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