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Coordinated histone modifications mediated by a CtBP co-repressor complex

Yujiang Shi1, Jun-ichi Sawada, Guangchao Sui

  • 1Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. yang_shi@hms.harvard.edu

Nature
|April 18, 2003
PubMed

Insights

The C-terminal binding protein (CtBP) complex mediates gene repression through DNA targeting and histone modification. This mechanism is crucial for its role in oncogenesis and animal development.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • The transcriptional co-repressor C-terminal binding protein (CtBP) is involved in tumorigenesis and animal development.
  • CtBP is recruited to DNA via transcription factors with a PXDLS motif, but its precise function remains unclear.

Purpose of the Study:

  • To identify the molecular mechanism of CtBP-mediated gene repression.
  • To investigate CtBP's role in tumorigenesis.

Main Methods:

  • Identification of a CtBP complex with gene targeting and histone modification capabilities.
  • RNA-mediated interference to inhibit CtBP expression and associated activities.
  • Analysis of histone modifications at the E-cadherin promoter and reporter gene assays.

Main Results:

  • A CtBP complex capable of gene targeting and histone modification was identified.
  • Inhibition of CtBP led to altered histone modifications at the E-cadherin promoter.
  • Suppression of CtBP increased E-cadherin promoter activity.

Conclusions:

  • CtBP mediates transcriptional repression through coordinated gene targeting and histone modifications.
  • These findings elucidate a mechanism for CtBP's involvement in oncogenesis.

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