Here we show that the lymphoid lineage-determining factors Ikaros and Aiolo
s can function as strong transcriptional repressors. This function is media
ted through two repression domains and is dependent upon the promoter conte
xt and cell type, Repression by Ikaros proteins correlates with hypo-acetyl
ation of core histones at promoter sites and is relieved by histone deacety
lase inhibitors. Consistent with these findings, Ikaros and its repression
domains can interact in vivo and in vitro with the mSin3 family of co-repre
ssors which bind to histone deacetylases. Based on these and our recent fin
dings of associations between Ikaros and Mi-2-HDAC, we propose that Ikaros
family members modulate gene expression during lymphocyte development by re
cruiting distinct histone deacetylase complexes to specific promoters.