June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The transcription factor neural retina leucine zipper controls photoreceptor-specific expression of Reep6
Author Affiliations & Notes
  • Hong Hao
    Neurobiol, Neurodegnrtn & Rpr Lab, National Eye Institute, Bethesda, MD
  • Shobi Veleri
    Neurobiol, Neurodegnrtn & Rpr Lab, National Eye Institute, Bethesda, MD
  • Bo Sun
    Neurobiol, Neurodegnrtn & Rpr Lab, National Eye Institute, Bethesda, MD
  • Raman Sood
    National Human Genome Research Institute, Bethesda, MD
  • Paul Liu
    National Human Genome Research Institute, Bethesda, MD
  • Anand Swaroop
    Neurobiol, Neurodegnrtn & Rpr Lab, National Eye Institute, Bethesda, MD
  • Footnotes
    Commercial Relationships Hong Hao, None; Shobi Veleri, None; Bo Sun, None; Raman Sood, None; Paul Liu, None; Anand Swaroop, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2020. doi:
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      Hong Hao, Shobi Veleri, Bo Sun, Raman Sood, Paul Liu, Anand Swaroop; The transcription factor neural retina leucine zipper controls photoreceptor-specific expression of Reep6. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2020.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The transcription factor neural retina leucine zipper (NRL) is essential to specify rod photoreceptor cell fate during retina development, as targeted deletion of Nrl (-/-) in mice led to a complete absence of rod photoreceptors. Nrl -/- rod precursors fail to turn on rod genes and differentiate into functional cone photoreceptors. Previous ChIP-seq analysis of mouse retina revealed NRL binding to the intron of the receptor accessory protein 6 (Reep6). Our goal is to elucidate the mechanism of transcriptional regulation of the Reep6 gene and to understand the molecular mechanism of NRL action.

Methods: We performed morpholino experiments in zebra fish to test the functional relevance of Reep6 in retina development. To study the transcriptional regulation of Reep6 gene, we used a combined approach including rapid analysis of cDNA ends (5’-RACE), chromatin immunoprecipitation, luciferase reporter assay, promoter mapping in retina explant and in vivo shRNA analysis.

Results: Knockdown of Reep6 in zebrafish by morpholinos led to microphthalmia. NRL binding to the Reep6 intron enhanced its promoter activity in a luciferase reporter assay and also in a GFP reporter assay in retina explant.

Conclusions: Reep6 expression is controlled by NRL through an enhancer located within its intron. NRL direct target genes serve as excellent candidates for retinal disease gene discovery.

Keywords: 738 transcription • 539 genetics • 648 photoreceptors  
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