Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes

The Ikaros gene family encodes zinc finger DNA-binding proteins essential f or lineage determination and control of proliferation in the lymphoid syste m. Here, we report that, in the nucleus of a T cell, a major fraction of Ik aros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and h istone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reve al that Ikaros proteins are capable of targeting chromatin remodeling and d eacetylation complexes in vivo. We propose that the restructuring of chroma tin is a key aspect of Ikaros function in lymphocyte differentiation.