Drosophila Ebi mediates Snail-dependent transcriptional repression through HDAC3-induced histone deacetylation.
The Drosophila Snail protein is a transcriptional repressor that is necessary for mesoderm formation. Here, we identify the Ebi protein as an essential Snail co-repressor. In ebi mutant embryos, Snail target genes are derepressed in the presumptive mesoderm. Ebi and Snail interact both genetically and physically. We identify a Snail domain that is sufficient for Ebi binding, and which functions independently of another Snail co-repressor, Drosophila CtBP. This Ebi interaction domain is conserved among all insect Snail-related proteins, is a potent repression domain and is required for Snail function in transgenic embryos. In mammalian cells, the Ebi homologue TBL1 is part of the NCoR/SMRT-HDAC3 (histone deacetylase 3) co-repressor complex. We found that Ebi interacts with Drosophila HDAC3, and that HDAC3 knockdown or addition of a HDAC inhibitor impairs Snail-mediated repression in cells. In the early embryo, Ebi is recruited to a Snail target gene in a Snail-dependent manner, which coincides with histone hypoacetylation. Our results demonstrate that Snail requires the combined activities of Ebi and CtBP, and indicate that histone deacetylation is a repression mechanism in early Drosophila development.
Qi
Dai
D
Wenner-Gren Institute, Developmental Biology, Stockholm University, Stockholm, Sweden.
Bergman
Mattias
M
Aihara
Hitoshi
H
Nibu
Yutaka
Y
Mannervik
Mattias
M
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D004330:Drosophila / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D000099186:Histone Deacetylase 3
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins; D006655:Histone Deacetylases; D006657:Histones; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000099186:Histone Deacetylase 3; C119014:ebi protein, Drosophila; C000604451:sna protein, Drosophila