The Krüppel-associated box-containing zinc finger gene family (KRAB-ZNF) is one 
of the largest gene families of transcriptional factors in the human genome. 
Although the functions of most of these genes remain to be determined, it is 
known that KRAB-mediated transcriptional repression requires a direct 
interaction with the KAP1 co-repressor. By mammalian one- or two-hybrid 
experiments in HEK293 cells, we compared transcriptional repression activities 
of 61 human KRAB-ZNFs. The results showed that six SCAN-KRAB-containing ZNFs are 
KAP1-independent transcriptional repressors whose SCAN-KRAB domain is unable to 
associate with KAP1 despite retaining transcriptional repression activity. 
Transcriptional repression activities of the SCAN-KRAB domain of 
KAP1-independent KRAB-ZNFs are not influenced by depletion of endogenous KAP1 
levels by small interfering RNA. Although the mechanism by which 
KAP1-independent KRAB-ZNFs repress transcriptional activity remains to be 
elucidated, it appears that there may be a pathway for transcriptional 
repression that does not involve KAP1. These results provide new insight into 
the functions of the members of the KRAB-ZNF family.