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The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD(More)
BACKGROUND Normal hematopoietic development depends on the activity of the Ikaros transcription factor, which contains distinct zinc-finger domains that mediate DNA binding and protein dimerization. Mice homozygous for a transgene encoding a dominant-negative version of Ikaros that lacks the DNA-binding domain but not the dimerization domain have a more(More)
Here we show that the lymphoid lineage-determining factors Ikaros and Aiolos can function as strong transcriptional repressors. This function is mediated through two repression domains and is dependent upon the promoter context and cell type. Repression by Ikaros proteins correlates with hypo-acetylation of core histones at promoter sites and is relieved by(More)
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(More)
Lymphoid cell differentiation relies on precisely orchestrated gene activation and repression events. Gene targeting studies have demonstrated crucial roles for the transcription factors Ikaros and Aiolos in regulating multiple stages of B and T cell development. Recent experiments suggest that Ikaros and Aiolos set B cell antigen-receptor (BCR)- and(More)
Ikaros plays a key role in lymphocyte development and homeostasis by both potentiating and repressing gene expression. Here we show that Ikaros interacts with components of the SUMO pathway and is SUMOylated in vivo. Two SUMOylation sites are identified on Ikaros whose simultaneous modification results in a loss of Ikaros' repression function. Ikaros(More)
Ikaros and Aiolos are Kruppel zinc finger proteins that play key roles in hemo-lymphoid development and homeostasis. We have previously shown that they can repress transcription through the recruitment of histone deacetylases (HDACs). Here, we provide the first functional evidence that these proteins can also repress gene function in a manner that does not(More)
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(More)
Ikaros is essential for the normal development and regulated proliferation of lymphoid cells. In lymphocytes, Ikaros exists as an integral component of chromatin-remodeling complexes, including the Mi-2beta/nucleosome remodeling and deacetylation complex (NuRD) complex. It is expected that Ikaros, together with these associated activities effects(More)
In yeast, INO1 and CHO2 gene expression is subject to repression in response to inositol and choline supplementation. The response by both genes to inositol is controlled by a single set of regulatory factors and the highly conserved and repeated UASINO element (consensus: 5' CATGTGAAAT 3') that is found in multiple copies in both promoters. However, none(More)