Stage-specific repression by the EKLF transcriptional activator.
Dynamic changes in transcription factor function can be mediated by switching its interaction with coactivators and corepressors. Erythroid Kruppel-like factor (EKLF) is an erythroid cell-specific transcription factor that plays a critical role in beta-globin gene activation via its interactions with CBP/p300 and SWI/SNF proteins. Unexpectedly, it also interacts with Sin3A and histone deacetylase 1 (HDAC1) corepressors via its zinc finger domain. We now find that selected point mutants can uncouple activation and repression and that an intact finger structure is not required for interactions with Sin3A/HDAC1 or for transrepression. Most intriguingly, EKLF repression exhibits stage specificity, with reversible EKLF-Sin3A interactions playing a key role in this process. Finally, we have located a key lysine residue that is both a substrate for CBP acetylation and required for Sin3A interaction. These data suggest a model whereby the stage of the erythroid cell alters the acetylation status of EKLF and plays a critical role in directing its coactivator-corepressor interactions and downstream transcriptional effects.
Chen
Xiaoyong
X
Mount Sinai School of Medicine, Brookdale Department of Molecular, Cell and Developmental Biology, Box 1020, One Gustave L. Levy Place, New York, NY 10029, USA.
Bieker
James J
JJ
D000818:Animals; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D050881:E1A-Associated p300 Protein; D017930:Genes, Reporter; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D013329:Structure-Activity Relationship; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D015534:Trans-Activators; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D004247:DNA; D008156:Luciferases; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D008239:Lysine