ChREBP has emerged as one of the key controllers of hepatic lipogenesis. While the function of ChREBP has been extensively investigated, mechanisms underlying its transcriptional regulation remain largely unknown. We located a conserved POU-binding site within mammalian ChREBP promoters, and demonstrated that the POU homeodomain protein Oct-1 binds to this site in the human HepG2 cell line. Oct-1 transfection significantly repressed ChREBP promoter activity 50-75%. Conversely, knockdown of Oct-1 expression with shRNA significantly increased ChREBP expression levels. Furthermore, insulin treatment resulted in a two-fold activation of ChREBP promoter activity, and stimulated endogenous ChREBP expression. We found that the stimulatory effect of insulin on the ChREBP promoter is at least partially dependent on the presence of the POU-binding site, and that insulin treatment reduced Oct-1 expression. Our observations identify Oct-1 as a transcriptional repressor of ChREBP, and suggest that insulin stimulates ChREBP expression via attenuating the repressive effect of Oct-1.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18859 |
| Date | 15 February 2010 |
| Creators | Sirek, Adam |
| Contributors | Ng, Dominic, Jin, Tianru |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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