Involvement of retinoic acid/retinoid receptors in the regulation of murine alphaB-crystallin/small heat shock protein gene expression in the lens

J Biol Chem. 1998 Jul 10;273(28):17954-61. doi: 10.1074/jbc.273.28.17954.


Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. We showed previously that Pax-6 can activate the alphaB-crystallin/small heat shock protein promoter via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46). Here we demonstrate that retinoic acid can induce the accumulation of alphaB-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of alphaB-promoter in the transfected lens cells. Thus, the alphaB-crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation.

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Crystallins / genetics*
  • DNA, Complementary
  • Gene Expression Regulation / physiology*
  • Heat-Shock Proteins / genetics*
  • Lens, Crystalline / metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • RNA, Messenger / genetics
  • Receptors, Retinoic Acid / physiology*
  • Transfection
  • Tretinoin / physiology*


  • Crystallins
  • DNA, Complementary
  • Heat-Shock Proteins
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Tretinoin