Kraus, Dominik and Karlstetter, Marcus and Walczak, Yana and Hilfinger, Daniela and Langmann, Thomas and Weber, Bernhard H. F. (2011) Retinal expression of the X-linked juvenile retinoschisis (RS1) gene is controlled by an upstream CpG island and two opposing CRX-bound regions. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 1809 (4-6). pp. 245-254. ISSN 1874-9399,
Full text not available from this repository. (Request a copy)Abstract
X-linked juvenile retinoschisis (XLRS) is an orphan retinal disease in males caused by mutations in the RS1 gene. Previously we have characterized cone-rod homeobox (CRX)-responsive elements in the promoter region of RS1 driving selective gene expression in the retina. Here, we expanded our identification and functional analysis of cis-regulatory elements controlling quantitative expression of RS1 in vitro and in vivo. Sequence analysis identified a CpG island 3 kb upstream of the transcription start site (TSS). In addition, chromatin immunoprecipitation coupled to microarrays (ChIP-Chip) targeting the retinal transcription factor CRX was performed. Thereby, we identified a second CRX-bound region (CBR2) in the first intron of RS1 which contains six evolutionarily conserved CRX binding motifs. In vitro luciferase reporter gene assays and dsRed reporter electroporation of mouse retinal organ cultures demonstrated a strong constitutive and orientation-independent enhancing effect of the upstream CpG island. The intronic CBR2 potently suppressed CBR1-driven RS1 promoter activity in vitro but failed to regulate a CBR1-reporter in short-term cultured mouse retinae. We conclude that a CpG island enhancer and two CBRs may act in a combinatorial fashion to fine-tune RS1 transcript levels in the retina. (C) 2011 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTOR-BINDING; DNA METHYLATION PATTERNS; CHIP-SEQ REVEALS; NATURAL-HISTORY; HOMEOBOX GENE; MOUSE MODEL; PHOTORECEPTOR; PROTEIN; CELLS; THERAPY; X-linked juvenile retinoschisis; RS1 gene; cis-regulatory elements; CRX-responsive element; CpG island |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jun 2020 08:22 |
| Last Modified: | 23 Jun 2020 08:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21069 |
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