Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins.
The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF-1 functions in part by binding to and transactivating the promoters of both the growth hormone (GH) and prolactin (PRL) genes and that of the GHF1 gene itself. We describe a naturally occurring isoform of GHF-1, GHF-2, in which an additional 26 amino acids are inserted into the activation domain of the protein as a result of alternative splicing. GHF-2 retains the DNA binding activity of GHF-1 and can activate the GH promoter but has lost the ability to activate the PRL and GHF1 promoters. These results suggest that GHF-2 may function in differential target gene activation during differentiation of the somatotrophic lineage. Both GHF-1 and GHF-2 transcripts are specifically expressed in the anterior pituitary. Analysis of the genomic GHF1 gene shows that most of the distinct functional domains of GHF-1 (and GHF-2) are encoded by separate exons. Gene segment duplication and exon shuffling may have contributed to the evolution of this cell type-specific transcriptional regulatory gene.
Theill
L E
LE
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Hattori
K
K
Lazzaro
D
D
Castrillo
J L
JL
Karin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D015723:Gene Library; D005796:Genes; D013006:Growth Hormone / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D010902:Pituitary Gland / Q000502:physiology*; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; C494186:Pou1f1 protein, rat; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D013006:Growth Hormone