Identification of a novel zinc finger protein binding a conserved element critical for Pit-1-dependent growth hormone gene expression.
Open Access
- 1 September 1993
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 7 (9) , 1674-1687
- https://doi.org/10.1101/gad.7.9.1674
Abstract
The growth hormone (GH) and prolactin genes require the pituitary-specific POU domain transcription factor Pit-1 for their activation. However, additional factors are necessary for the effective expression of these genes. Analysis of evolutionarily conserved sequences in the proximal GH promoter suggests the critical importance of one highly conserved element located between the two Pit-1 response elements. Mutation of this site decreases expression of a transgene in mice > 100-fold. We have identified a major activity binding to this site as a novel member of the Cys/His zinc finger superfamily, referred to as Zn-15. The Zn-15 DNA-binding domain comprises three zinc fingers separated by unusually long linker sequences that would be expected to interrupt specific DNA site recognition. Zn-15 synergizes with Pit-1 to activate the GH promoter in heterologous cell lines in which this promoter is only minimally responsive to Pit-1 alone. Our data suggest that functional interactions between the tissue-specific POU domain factor Pit-1 and this novel zinc finger factor binding to an evolutionarily conserved region in the GH promoter may constitute an important component of the combinatorial code that underlies the effective expression of the GH gene.Keywords
This publication has 37 references indexed in Scilit:
- Synergistic interactions between Pit-1 and other elements are required for effective somatotroph rat growth hormone gene expression in transgenic miceMolecular Endocrinology, 1993
- RNA and DNA binding zinc fingers in Xenopus TFIIIACell, 1992
- A Mutation in the POU-Homeodomain of Pit-1 Responsible for Combined Pituitary Hormone DeficiencyScience, 1992
- Anterior pituitary development: Short tales from dwarf miceCell, 1992
- Molecular cloning of cDNAs encoding the GAP-associated protein p190: Implications for a signaling pathway from ras to the nucleusCell, 1992
- Cretinism with combined hormone deficiency caused by a mutation in the PIT1 geneNature Genetics, 1992
- Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1Nature, 1990
- Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors.Genes & Development, 1990
- A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotypeCell, 1988
- The pituitary-specific transcription factor GHF-1 is a homeobox-containing proteinCell, 1988