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Dissection of functional domains of the pituitary-specific transcription factor GHF-1

Nature volume 342, pages 945–948 (1989)Cite this article

Abstract

THE specific expression of growth hormone (GH) in the somatotrophic cells of the anterior pituitary is largely attributable to a short promoter in the 5' flanking region of the GH gene1–6. This promoter contains two binding sites for the transcription factor GHF-1 (refs 3,7), the expression of which is also specific to cells of the somatotrophic lineage8,9 and correlates with activation of the GH gene in the developing mouse pituitary9. Various studies indicate that GHF-1 is the main determinant of cell type-specific expression of the GH gene3–9. GHF-1 is a member of the POU-domain class of proteins that each contain two highly conserved sequence motifs, the homoeodomain and the POU-specific domain8,10,11. Here we report that the GHF-1 homoeodomain is sufficient for sequence-specific DNA binding, although its activity is stimulated by the POU-specific domain, which does not interact directly with the DNA. Transcriptional activation is mediated by a separate domain rich in hydroxylated amino-acid residues. Similar sequences are present in other cell type-specific transcription factors.

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Authors and Affiliations

  1. Department of Pharmacology, M-036, School of Medicine, Center for Molecular Genetics, University of California, San Diego, La Jolla, California, 92093, USA

    Lars E. Theill, José-Luis Castrillo, David Wu & Michael Karin

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  1. Lars E. Theill
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  2. José-Luis Castrillo
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  3. David Wu
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  4. Michael Karin
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Theill, L., Castrillo, JL., Wu, D. et al. Dissection of functional domains of the pituitary-specific transcription factor GHF-1. Nature 342, 945–948 (1989). https://doi.org/10.1038/342945a0

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