Conserved interaction between distinct Kruppel-associated box domains and the transcriptional intermediary factor 1 beta

The Kruppel-associated box (KRAB) domain, originally identified as a 75-aa sequence present in numerous Kruppel-type zinc-finger proteins, is a potent DNA-binding-dependent transcriptional repression domain that is believed t o function through interaction with the transcriptional intermediary factor 1 (TIF1) beta. On the basis of sequence comparison and phylogenetic analys is, we have recently defined three distinct subfamilies of KRAB domains. In the present study, individual members of each subfamily were tested for tr anscriptional repression and interaction with TIF1 beta and two other close ly related family members (TIF1 alpha and TIF1 gamma). All KRAB variants we re shown, (i) to repress transcription when targeted to DNA through fusion to a heterologous DNA-binding domain in mammalian cells, and (ii) to intera ct specifically with TIF1 beta, but not with TIF1 alpha Or TIF1 gamma. Take n together, these results implicate TIF1 beta as a common transcriptional c orepressor for the three distinct subfamilies of KRAB zinc-finger proteins and suggest a high degree of conservation in the molecular mechanism underl ying their transcriptional repression activity.