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. 2002 Aug 2;277(31):27697-705.
doi: 10.1074/jbc.M201694200. Epub 2002 May 15.

A molecular dissection of the repression circuitry of Ikaros

Joseph Koipally  1 , Katia Georgopoulos
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Free article

A molecular dissection of the repression circuitry of Ikaros

Joseph Koipally et al. J Biol Chem. .
Free article

Abstract

Ikaros is a key regulator of the hemo-lymphoid system in which it is presumed to function by both potentiating and repressing gene expression. Repression is mediated through two independent domains at the N and C terminus of the protein, both of which can independently recruit the corepressors Mi-2beta, Sin3A, and Sin3B and the Class I histone deacetylases 1 and 2; the N-terminal domain can also associate with the corepressor CtBP. Here we describe a detailed dissection of these two domains and identify the minimal repression modules and the corepressor requirements for their activity. Based on these studies, we describe mutations in a full-length Ikaros protein that abrogate interactions with each of the identified corepressors and abolish the protein's function as a repressor. Finally, we show that, barring CtBP, the Ikaros family members Aiolos, Helios, and Eos can associate with all of the identified corepressors of Ikaros including its newly identified interactors, Class II HDACs.

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