December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Transcriptional Regulation of the Mouse aA-crystallin Locus
Author Affiliations & Notes
  • A Cvekl
    Ophth & Vis Sci & Mol Genetics Albert Einstein College of Med Bronx NY
  • Y Yang
    Molecular Genetics
    Albert Einstein College of Medicine Bronx NY
  • BK Chauhan
    Ophthalmology and Visual Sciences
    Albert Einstein College of Medicine Bronx NY
  • S Goswami
    Ophthalmology and Visual Sciences
    Albert Einstein College of Medicine Bronx NY
  • K Cveklova
    Ophthalmology and Visual Sciences
    Albert Einstein College of Medicine Bronx NY
  • K Montgomery
    Molecular Genetics
    Albert Einstein College of Medicine Bronx NY
  • R Kucherlapati
    Molecular Genetics
    Albert Einstein College of Medicine Bronx NY
  • Footnotes
    Commercial Relationships   A. Cvekl, None; Y. Yang, None; B.K. Chauhan, None; S. Goswami, None; K. Cveklova, None; K. Montgomery, None; R. Kucherlapati, None. Grant Identification: NIH Grants EY12200, EY00484, EY13022 and RPB,Inc.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3658. doi:
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    • Get Citation

      A Cvekl, Y Yang, BK Chauhan, S Goswami, K Cveklova, K Montgomery, R Kucherlapati; Transcriptional Regulation of the Mouse aA-crystallin Locus . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3658.

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

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Abstract

Abstract: : Purpose: αA-crystallin is expressed in lens epithelium and fibers. Dramatic induction of αA-crystallin expression is observed at the onset of lens fiber cell differentiation. The widely used promoter fragments, i.e. -366/+46 and -111/+46, to express transgenes are active only in lens fiber cells. This study seeks a) to identify distant control regions (DCRs) essential for high level of αA-crystallin expression in lens fibers and in lens epithelium and b) to perform fine mapping of regulatory sites present in the -111 to +46 promoter fragment. Methods: A mouse BAC clone containing the αA-crystallin locus from RP23 C57/BL6/J genomic library was isolated and sequenced. Multiple sequence alignments (MSA) of different genomic loci (human, mouse, chicken, hamster, and mole rat) were used to predict non-coding conserved sequences. Transient transfections were conducted in cultured lens and non-lens cells using the candidate DCRs combined with the -111 to +46 promoter fragment. Protein-DNA binding studies were used to study binding of Pax6 and c-Maf. Results: MSA revealed at least six candidate DCRs. These DCRs contain arrays of putative transcription factor binding sites including c-Maf, Pax6, Prox1, CREB, RAR/RXR, Sp1 and AP2. Transient transfections have identified at least three DCRs activating the αA-crystallin promoter in lens cells but not in fibroblasts. The promoter fragment -111 to +46 contains three Pax6 and two c-Maf binding sites. Conclusion: We have identified several novel lens-specific distant control regions of the mouse αA-crystallin promoter. The -111 to +46 promoter fragment contains an array of regulatory sites interacting with Pax6, c-Maf and CREB.

Keywords: 604 transcription • 417 gene/expression • 476 molecular biology 
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