Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins

• Published in: The EMBO journal 1992-06, Vol.11 (6), p.2261-2269
• Main Authors: Theill, L.E., Hattori, K., Lazzaro, D., Castrillo, J.L., Karin, M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Biological and medical sciences; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fetus; Fundamental and applied biological sciences. Psychology; Gene Library; Genes; GHF-2 protein; Growth Hormone - genetics; Introns; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; mRNA; nucleotide sequence; Oligodeoxyribonucleotides; Phenotype; Pituitary Gland - physiology; prediction; Prolactin - genetics; Promoter Regions, Genetic; Rats; Restriction Mapping; RNA Splicing; Sequence Homology, Nucleic Acid; splicing; Transcription Factor Pit-1; transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transfection
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1992.tb05285.x

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.