Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter its DNA-binding specificity

Galina N. Filippova, Jonathan E. Ulmer, James M. Moore, Michael D. Ward, Ying J. Hu, Paul E. Neiman, Steven J. Collins, Chen Feng Qi, Dmitri I. Loukinov, Elena M. Pugacheva, Herbert C. Morse, Victor V. Lobanenkov, Elena M. Klenova, Paul E. Grundy, Andrew P. Feinberg, Anne Marie Cleton-Jansen, Elna W. Moerland, Cees J. Cornelisse, Hiroyoshi Suzuki, Akira KomiyaAnnika Lindblom, Françoise Dorion-Bonnet

Research output: Contribution to journalArticlepeer-review

Abstract

CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that is involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Because CTCF targets include oncogenes and tumor suppressor genes, we screened over 100 human tumor samples for mutations that might disrupt CTCF activity. We did not observe any CTCF mutations leading to truncations/premature stops. Rather, in breast, prostate, and Wilms’ tumors, we observed four different CTCF somatic missense mutations involving amino acids within the ZF domain. Each ZF mutation abrogated CTCF binding to a subset of target sites within the promoters/insulators of certain genes involved in regulating cell proliferation but did not alter binding to the regulatory sequences of other genes. These observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function".

Original languageEnglish (US)
Pages (from-to)48-52
Number of pages5
JournalCancer Research
Volume62
Issue number1
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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