The FK506-binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1

EMBO J. 2001 Sep 3;20(17):4814-25. doi: 10.1093/emboj/20.17.4814.

Abstract

FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressants that belong to a subgroup of proteins, known as immunophilins, with peptidylprolyl cis-trans isomerase (PPIase) activity. Sequence comparison suggested that the HD2-type histone deacetylases and the FKBP-type PPIases may have evolved from a common ancestor enzyme. Here we show that FKBP25 physically associates with the histone deacetylases HDAC1 and HDAC2 and with the HDAC-binding transcriptional regulator YY1. An FKBP25 immunoprecipitated complex contains deacetylase activity, and this activity is associated with the N-terminus of FKBP25, distinct from the FK506/rapamycin-binding domain. Furthermore, FKBP25 can alter the DNA-binding activity of YY1. Together, our data firmly establish a relationship between histone deacetylases and the FKBP enzymes and provide a novel and critical function for the FKBPs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Consensus Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • Escherichia coli
  • Genes, Reporter
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • HeLa Cells
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases / metabolism*
  • Humans
  • Jurkat Cells
  • Kinetics
  • Luciferases / genetics
  • Nuclear Proteins / metabolism
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Tacrolimus Binding Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection
  • YY1 Transcription Factor

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human
  • FKBP3 protein, human
  • Luciferases
  • Glutathione Transferase
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases
  • Tacrolimus Binding Proteins