FOG-1 recruits the NuRD repressor complex to mediate transcriptional repression by GATA-1

• DOI: 10.1038/sj.emboj.7600703
• Publication Date: 2005-05-26T16:31:37Z
• Authors: Wei Hong; Minako Nakazawa; Ying-Yu Chen; Rajashree Kori; Christopher R Vakoc; Carrie Rakowski; Gerd A Blobel
• Keywords: 0303 health sciences; Amino Acid Motifs; Molecular Sequence Data; Nuclear Proteins; Histone Deacetylases; Protein Structure, Tertiary; DNA-Binding Proteins; Mice; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Chlorocebus aethiops; Animals; Erythroid-Specific DNA-Binding Factors; Point Mutation; GATA1 Transcription Factor; Amino Acid Sequence; Gene Silencing; Carrier Proteins; N-Glycosyl Hydrolases; Cells, Cultured; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Protein Binding

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.