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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Chlorocebus aethiops
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Erythroid-Specific DNA-Binding Factors
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GATA1 Transcription Factor
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Gene Silencing
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Histone Deacetylases / metabolism*
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Mice
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Molecular Sequence Data
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N-Glycosyl Hydrolases / genetics
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N-Glycosyl Hydrolases / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Point Mutation
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-kit / genetics
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Proto-Oncogene Proteins c-kit / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Sequence Homology, Amino Acid
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic*
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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GATA1 Transcription Factor
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Gata1 protein, mouse
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Nuclear Proteins
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Repressor Proteins
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Transcription Factors
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ZFPM1 protein, human
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Zfpm1 protein, mouse
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Proto-Oncogene Proteins c-kit
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N-Glycosyl Hydrolases
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NEIL3 protein, human
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Histone Deacetylases
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Mi-2 Nucleosome Remodeling and Deacetylase Complex