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 synergistic interactions with Pit-1, named for 15 DNA-binding zinc fingers, including 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-amino acid mouse protein is 89% identical to rat (r) Zn-15 overall, and is 97% 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 pituitary cDNAs were the same as the mouse (m) Zn-16; the rat sequence in GenBank 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 fingers 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 expression by RT-PCR showed that the mRNA is, produced at similar levels in normal and GH-deficient Ames dwarf (Prop-1 <df-/->) mouse pituitaries at postnatal day 1. Mouse Zn-16 mRNA also was detected by ribonuclease protection assay in the pre-somatotrophic mouse cell line GHFT1-5. The Zn-16 protein is bipartite in that the N-terminal half displays tandem spacing typical of most zinc finger proteins, while the C-terminal portion contains long linkers between fingers that cooperatively bind to a DNA response element. Expression in early postnatal pituitary and in pre-somatotrophic cells suggests that Zn-16 could play a role in pituitary development prior to somatotroph differentiation.
VanderHeyden
T C
TC
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118-5698, USA.
Wojtkiewicz
P W
PW
Voss
T C
TC
Mangin
T M
TM
Harrelson
Z
Z
Ahlers
K M
KM
Phelps
C J
CJ
Hurley
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics*; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C406423:Zfp292 protein, mouse; C489979:Zfp292 protein, rat; D013006:Growth Hormone