TY - JOUR
T1 - Involvement of retinoic acid/retinoid receptors in the regulation of murine αB-crystallin/small heat shock protein gene expression in the lens
AU - Gopal-Srivastava, Rashmi
AU - Cvekl, Ales
AU - Piatigorsky, Joram
PY - 1998/7/10
Y1 - 1998/7/10
N2 - 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 αB-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 αB-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 αB-promoter in the transfected lens cells. Thus, the αB- 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.
AB - 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 αB-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 αB-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 αB-promoter in the transfected lens cells. Thus, the αB- 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.
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U2 - 10.1074/jbc.273.28.17954
DO - 10.1074/jbc.273.28.17954
M3 - Article
C2 - 9651402
AN - SCOPUS:0032504158
SN - 0021-9258
VL - 273
SP - 17954
EP - 17961
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -