Ku80 gene expression is Sp1-dependent and sensitive to CpG methylation within a novel cis element

Dale L. Ludwig, Fanqing Chen, Scott R. Peterson, Andre Nussenzweig, Gloria C. Li, David J. Chen

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The Ku70/80 complex, known as Ku, constitutes the DNA end binding component of the DNA-dependent protein kinase (DNA-PK). We have characterized the promoter region of the mouse and human Ku80 genes to delineate transcriptional elements necessary for basal gene expression and proliferation-dependent regulation. Consensus Sp1 recognition elements were identified in both promoters, and were determined to be essential for basal expression. We further identified a near-perfect palindrome of 21 base pairs located immediately 5' to one Sp1 element. This sequence was present once within the mouse Ku80 promoter and seven times, in a head-to-tail tandem array, within the human Ku80 promoter. This sequence possessed homology with a methylationsensitive promoter element, Enh2, present in the LTR of mouse intractisternal A-particles. Promoter deletion studies and expression analysis of in-vitro methylated reporter gene constructs provided strong evidence that, in vivo, this repeat sequence regulates Ku80 gene expression in cis, through a mechanism involving CpG methylation. Evidence is also presented, suggesting that Ku is directly involved in this regulatory process.

Original languageEnglish (US)
Pages (from-to)181-194
Number of pages14
JournalGene
Volume199
Issue number1-2
DOIs
StatePublished - Oct 15 1997

Keywords

  • DNA-dependent protein kinase
  • Dna repair
  • Transcription
  • V(D)J recombination

ASJC Scopus subject areas

  • Genetics

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    Ludwig, D. L., Chen, F., Peterson, S. R., Nussenzweig, A., Li, G. C., & Chen, D. J. (1997). Ku80 gene expression is Sp1-dependent and sensitive to CpG methylation within a novel cis element. Gene, 199(1-2), 181-194. https://doi.org/10.1016/S0378-1119(97)00366-1