GENES: STRUCTURE AND REGULATION
Ikaros Interactions with CtBP Reveal a Repression Mechanism That Is Independent of Histone Deacetylase Activity*

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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.

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Published, JBC Papers in Press, April 13, 2000, DOI 10.1074/jbc.M000254200

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This work was supported in part by National Institutes of Health Grant RO1 AI33062 (to K. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Supported by an Howard Hughes Medical Institute predoctoral fellowship. Present address: Graduate program in Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.