Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3

Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3

Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612; and Center for Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX 78245

Abstract

YY1 is a mammalian zinc-finger transcription factor with unusual structural and functional features. It has been implicated as a positive and a negative regulatory factor that binds to the CCATNTT consensus DNA element located in promoters of many cellular and viral genes. A mammalian cDNA that encodes a YY1-binding protein and possesses sequence homology with the yeast transcriptional factor RPD3 has been identified. A Gal4 DNA binding domain–mammalian RPD3 fusion protein strongly represses transcription from a promoter containing Gal4 binding sites. Association between YY1 and mammalian RPD3 requires a glycine-rich region on YY1. Mutations in this region abolish the interaction with mammalian RPD3 and eliminate transcriptional repression by YY1. These data suggest that YY1 negatively regulates transcription by tethering RPD3 to DNA as a cofactor and that this transcriptional mechanism is highly conserved from yeast to human.

Footnotes

↵ * To whom reprint requests should be addressed.
Robert P. Perry, Fox Chase Cancer Center, Philadelphia, PA
Abbreviations: GST, glutathione S-transferase; SV40, simian virus 40; mRPD3, mouse RPD3.

Data deposition: The sequences reported in this paper have been deposited in the GenBank data base (accession nos. U31758U31758 and U31814U31814, respectively, for the mouse and human RPD3 cDNAs).