Dissection of functional domains of the pituitary-specific transcription factor GHF-1.
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 gene. This promoter contains two binding sites for the transcription factor GHF-1, the expression of which is also specific to cells of the somatotrophic lineage and correlates with activation of the GH gene in the developing mouse pituitary. Various studies indicate that GHF-1 is the main determinant of cell type-specific expression of the GH gene. 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 domain. 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.
Theill
L E
LE
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Castrillo
J L
JL
Wu
D
D
Karin
M
M
D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D005801:Genes, Homeobox; D005822:Genetic Vectors; D013006:Growth Hormone / Q000235:genetics*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D011993:Recombinant Fusion Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D013006:Growth Hormone