Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity.
We have previously shown that Ikaros can repress transcription through the recruitment of histone deacetylase complexes. Here we provide evidence that Ikaros can also repress transcription through its interactions with the co-repressor, C-terminal binding protein (CtBP). CtBP interacts with Ikaros isoforms through a PEDLS motif present at the N terminus of these proteins but not with homologues like Aiolos which lack this motif. Mutations in Ikaros that prevent CtBP interactions reduce its ability to repress transcription. CtBP interacts with Sin3A but not with the Mi-2 co-repressor and it represses transcription in a manner that is independent of histone deacetylase activity. These data strongly suggest that CtBP contributes to a histone deacetylase activity independent mechanism of repression by Ikaros. Finally, we show that the viral oncoprotein E1A, which binds to CtBP, also shows a strong association with Ikaros. This Ikaros-E1A interaction may underlie Ikaros's decreased ability to repress transcription in E1A transformed cells.
Koipally
J
J
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Georgopoulos
K
K
D016475:3T3 Cells; D000251:Adenosine Triphosphatases; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins; D002460:Cell Line; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051740:Ikaros Transcription Factor; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011233:Precipitin Tests; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D017500:Adenovirus E1A Proteins; D001324:Autoantigens; C115323:CHD4 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497239:IKZF1 protein, human; C116095:Mi-2 protein, Drosophila; D010750:Phosphoproteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D005982:Glutathione Transferase; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases