Krüppel-associated boxes are potent transcriptional repression domains

Proc Natl Acad Sci U S A. 1994 May 10;91(10):4509-13. doi: 10.1073/pnas.91.10.4509.


The Krüppel-associated box (KRAB) is a highly conserved, 75-aa region containing two predicted amphipathic alpha-helices. The KRAB domain is present in the amino-terminal regions of more than one-third of all Krüppel-class Cys2His2 zinc finger proteins and is conserved from yeast to man; however, its function is unknown. Here it is shown that the KRAB domain functions as a DNA binding-dependent transcriptional repressor when fused to a heterologous DNA-binding domain from the yeast GAL4 protein. A 45-aa segment containing one of the predicted KRAB amphipathic helices was necessary and sufficient for repression. Amino acid substitutions in the predicted helix abolished the repression function. These results assign a function, transcriptional repression, to the highly conserved KRAB box and define a minimal repression domain which may aid in identifying mechanisms of repression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / biosynthesis
  • Fungal Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Polymerase Chain Reaction
  • Protein Structure, Secondary*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism*
  • Restriction Mapping
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection
  • Zinc Fingers / genetics


  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Kruppel-Like Transcription Factors
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors