Identification and characterization of two novel human SCAN domain-containing zinc finger genes ZNF396 and ZNF397.

We have identified two novel human SCAN domain genes ZNF396 and ZNF397, which are clustered within the region of chromosome 18q12. Three isoforms of ZNF396 transcript, 1.5, 2.5 and 3.9-kb, are expressed highly in liver. Four isoforms of ZNF397 transcript, 1.7, 2.5, 7.0 and 9.0-kb, are expressed in a variety of tissues, with varying levels. The SCAN-(C(2)H(2))(X) genes encode two distinct proteins due to a unique alternative splicing mechanism. Both ZNF396-fu (full zinc fingers) and ZNF397-fu consist of a SCAN domain in the N-terminal region and many consecutive C(2)H(2) zinc finger repeats in the C-terminal region. ZNF396-nf (no zinc fingers) and ZNF397-nf encode 210 and 198 amino acids, respectively, containing the SCAN domain only. ZNF396-fu, ZNF396-nf, ZNF397-fu or ZNF397-nf can homo-associate, while ZNF396-fu hetero-associates with ZNF396-nf, and ZNF397-fu hetero-associates with ZNF397-nf. ZNF396-nf and ZNF397-nf polypeptides are expressed diffusely in the cells, while ZNF396-fu and ZNF397-fu polypeptides target specifically to the nuclei. ZNF396-fu, ZNF396-nf and ZNF397-nf can repress reporter gene transcription, with ZNF397-nf having the strongest repression activity. Deletion analysis revealed that ZNF397-fu is a transcriptional activator without its nine zinc finger repeats.