A novel human KRAB-containing zinc-finger gene ZNF446 inhibits transcriptional activities of SRE and AP-1.

Kruppel-related zinc-finger proteins constitute the largest individual family of transcription factors in mammals [C. Looman, L. Hellman, M. Abrink, A novel Kruppel-associated box identified in a panel of mammalian zinc-finger proteins, Mammalian Genome 15 (1) (2004) 35-40.[1]]. Here we identified and characterized a novel zinc-finger gene named ZNF446. The predicted protein contains a KRAB and three C(2)H(2) zinc fingers. Northern blot analysis shows that ZNF446 is expressed in a variety of human adult tissues with the highest expression level in muscle. ZNF446 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16. Overexpression of ZNF446 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, in which the KRAB motif represents the basal transcriptional repressive activity, suggesting that the ZNF446 protein may act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular functions.