Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells

Y. Kang, J. A. Hong, G. A. Chen, D. M. Nguyen, D. S. Schrump

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Previously, we reported that the paralogous zinc-finger proteins - CTCF and brother of the regulator of imprinted sites (BORIS), directly contribute to transcriptional regulation of NY-ESO-1 in lung cancer cells. To further examine mechanisms that mediate expression of this cancer-testis gene, we performed software-guided analysis of the NY-ESO-1 promoter region, which revealed several potential Sp1-binding motifs. Sequential 5-aza-2′deoxycytidine/ depsipeptide FK228 treatment markedly induced BORIS expression and enhanced nuclear translocation of Sp1 in lung cancer cells. Transient transfection assays using promoter-reporter constructs, as well as gel-shift and chromatin immunoprecipitation experiments revealed that NY-ESO-1 promoter activity coincided with occupancy of the proximal Sp1-binding site in lung cancer cells. Mutations within the Sp1 recognition sequence specifically eliminated binding of Sp1 to this motif in vitro, and markedly diminished NY-ESO-1 promoter activity in vivo. siRNA-mediated inhibition of Sp1 expression decreased NY-ESO-1 promoter activity, whereas knock down of CTCF expression augmented NY-ESO-1 transcription in lung cancer cells. Co-immunoprecipitation experiments indicated that Sp1 physically interacts with BORIS but not with CTCF in vivo. Collectively, these findings suggest that BORIS recruits Sp1 to mediate de-repression of NY-ESO-1 during pulmonary carcinogenesis.

Original languageEnglish (US)
Pages (from-to)4394-4403
Number of pages10
JournalOncogene
Volume26
Issue number30
DOIs
StatePublished - Jun 28 2007
Externally publishedYes

Keywords

  • BORIS
  • CTCF
  • Epigenetics
  • Lung cancer
  • NY-ESO-1
  • Sp1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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