Transcriptional intermediary factors (TIFs) are a group of transcriptional coactivators and corepressors that regulate gene expression by modulating chromatin structure and assembly of transcription initiation complexes. TIF1beta is a member of the TIF1 subfamily of chromatin-associated TIFs that play a key role in many developmental and physiological processes. Studies using knockout mice reveal the important function of TIF1beta in regulating genomic imprinting, T cell activation, and T cell tolerance.