The protein CTCF is required for the enhancer blocking activity of vertebrate insulators

Cell. 1999 Aug 6;98(3):387-96. doi: 10.1016/s0092-8674(00)81967-4.


An insulator is a DNA sequence that can act as a barrier to the influences of neighboring cis-acting elements, preventing gene activation, for example, when located between an enhancer and a promoter. We have identified a 42 bp fragment of the chicken beta-globin insulator that is both necessary and sufficient for enhancer blocking activity in human cells. We show that this sequence is the binding site for CTCF, a previously identified eleven-zinc finger DNA-binding protein that is highly conserved in vertebrates. CTCF sites are present in all of the vertebrate enhancer-blocking elements we have examined. We suggest that directional enhancer blocking by CTCF is a conserved component of gene regulation in vertebrates.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • CCCTC-Binding Factor
  • Cell Nucleus / metabolism
  • Chickens
  • Conserved Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Deoxyribonuclease I
  • Enhancer Elements, Genetic*
  • Genetic Variation
  • Globins / genetics
  • Humans
  • K562 Cells
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism
  • Protein Biosynthesis
  • Repressor Proteins*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Vertebrates
  • Zinc Fingers


  • CCCTC-Binding Factor
  • CTCF protein, human
  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides
  • Repressor Proteins
  • Transcription Factors
  • Globins
  • Deoxyribonuclease I