Mouse growth hormone transcription factor Zn-16: unique bipartite structure containing tandemly repeated zinc finger domains not reported in rat Zn-15

Rat Zn-15 is a transcription factor activating GH gene expression by synerg istic interactions with Pit-1, named for 15 DNA-binding zinc fingers, inclu ding fingers IX, X, and XI that are responsible for GH promoter binding. In this study, a mouse cDNA for Zn-15 was characterized. The predicted 2192-a mino acid mouse protein is 89% identical to rat (r) Zn-15 overall, and is 9 7% similar in the C-terminal domain necessary for binding the GH promoter. However, the mouse cDNA encodes 16 zinc fingers, and sequences of rZn-15 pi tuitary cDNAs were the same as the mouse (m) Zn-16; the rat sequence in Gen Bank has a one nucleotide offset of a 17-bp segment in the finger V region. The mouse and corrected rat sequences contain four tandemly repeated finge rs in the N-terminus, each separated by seven amino acids, typical of zinc finger proteins of the transcription factor IIIA-type. Analysis of mZn-16 e xpression by RT-PCR showed that the mRNA is produced at similar levels in n ormal and GH-deficient Ames dwarf (Prop-1 < df-/- >) mouse pituitaries at p ostnatal day 1. Mouse Zn-16 mRNA also was detected by ribonuclease protecti on assay in the pre-somatotrophic mouse cell line GHFT1-5. The Zn-16 protei n is bipartite in that the N-terminal half displays tandem spacing typical of most zinc finger proteins, while the C-terminal portion contains long li nkers between fingers that cooperatively bind to a DNA response element. Ex pression in early postnatal pituitary and in pre-somatotrophic cells sugges ts that Zn-16 could play a role in pituitary development prior to somatotro ph differentiation. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.