April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Hypoxia-Induced De-SUMOylaiton of CTCF Controls Pax6 Activity in Corneal Epithelial Cells
Author Affiliations & Notes
  • L. Lu
    Medicine, David Geffen Sch of Med/UCLA, Torrance, California
  • J. Wang
    Medicine, David Geffen Sch of Med/UCLA, Torrance, California
  • Footnotes
    Commercial Relationships  L. Lu, None; J. Wang, None.
  • Footnotes
    Support  NIH-EY15281
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1958. doi:
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      L. Lu, J. Wang; Hypoxia-Induced De-SUMOylaiton of CTCF Controls Pax6 Activity in Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1958.

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

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Purpose: : Previous studies revealed that activity of CTCF significantly decreased in response to stress stimulation. Purpose of the present study is to demonstrate that there is a markedly diminished SUMO modification of CTCF in response to hypoxic and oxidative stress stimulation affecting Pax6 activity in corneal epithelial fate.

Methods: : HCE and HEK293 cells were maintained in 37 °C incubator supplied with 5% CO2. Cells were exposed to 1% oxygen (hypoxic stress) or 1 mM hydrogen peroxide (oxidative stress). The SUMO modification of CTCF was examined by immunoprecipitation and Western analysis. Downstream CTCF-targeting gene alterations were determined by real-time PCR and luciferase reporter assay.

Results: : We found that CTCF was modified by SUMO modification in the post-translational level. The Lys-74 and Lys-689 were found to be the major sites for CTCF SUMOylation. The SUMOylated-CTCF is sensitive to both hypoxic and oxidative stimuli. Our data demonstrated: 1) hypoxic and oxidative treatments induced a rapid de-SUMOylation of CTCF; 2) MG132, a proteasome inhibitor, mimicked the oxidative stress-induced effect on SUMOylated-CTCF; 3) the stability and sub-cellular localization of sentrin/SUMO-specific proteases (SENPs) were sensitive to hypoxic and oxidative treatments; 4) SUMO modification of CTCF was required for its ability to control Pax6 actvity; and 5) altered Pax6 gene expression induced by hypoxia was attributed to the de-SUMOylation of CTCF.

Conclusions: : Hypoxic and oxidative stresses induce de-SUMOylation of CTCF to regulate Pax6 gene expression. We conclude that the de-SUMOylation is a novel mechanism that involves physiological function of CTCF in response to environmental stresses.

Keywords: cornea: epithelium • hypoxia • genetics 

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