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

FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressant s that belong to a subgroup of proteins, known as immunophilins, with pepti dylprolyl cis-trans isomerase (PPIase) activity. Sequence comparison sugges ted that the HD2-type histone deacetylases and the FKBP-type PPIases may ha ve evolved from a common ancestor enzyme. Here we show that FKBP25 physical ly associates with the histone deacetylases HDAC1 and HDAC2 and with the HD AC-binding transcriptional regulator YY1. An FKBP25 immunoprecipitated comp lex contains deacetylase activity, and this activity is associated with the N-terminus of FKBP25, distinct from the FK506/rapamycin-binding domain. Fu rthermore, FKBP25 can alter the DNA-binding activity of YY1. Together, our data firmly establish a relationship between histone deacetylases and the F KBP enzymes and provide a novel and critical function for the FKBPs.