FOG-1 Recruits the NuRD Repressor Complex to Mediate Transcriptional Repression by GATA-1

EMBO J. 2005 Jul 6;24(13):2367-78. doi: 10.1038/sj.emboj.7600703. Epub 2005 May 26.

Abstract

Transcription factor GATA-1 and its cofactor FOG-1 coordinate erythroid cell maturation by activating erythroid-specific genes and repressing genes associated with the undifferentiated state. Here we show that FOG-1 binds to the NuRD corepressor complex in vitro and in vivo. The interaction is mediated by a small conserved domain at the extreme N-terminus of FOG-1 that is necessary and sufficient for NuRD binding. This domain defines a novel repression module found in diverse transcriptional repressors. NuRD is present at GATA-1/FOG-1-repressed genes in erythroid cells in vivo. Point mutations near the N-terminus of FOG-1 that abrogate NuRD binding block gene repression by FOG-1. Finally, the ability of GATA-1 to repress transcription was impaired in erythroid cells expressing mutant forms of FOG-1 that are defective for NuRD binding. Together, these studies show that FOG-1 and likely other FOG-like proteins are corepressors that link GATA factors to histone deacetylation and nucleosome remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gene Silencing
  • Histone Deacetylases / metabolism*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Mice
  • Molecular Sequence Data
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Point Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • ZFPM1 protein, human
  • Zfpm1 protein, mouse
  • Proto-Oncogene Proteins c-kit
  • FLJ10858 protein, human
  • N-Glycosyl Hydrolases
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex