Regulation of the pituitary-specific homeobox gene GHF1 by cell-autonomous and environmental cues

• Published in: Nature (London) 1990-06, Vol.345 (6278), p.829-832
• Main Authors: McCormick, Alison, Brady, Helen, Theill, Lars E, Karin, Michael
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding sites; Biochemical analysis; Biological and medical sciences; Cellular biology; Cloning, Molecular; Cyclic AMP; Cyclic AMP - physiology; Cyclic AMP response element-binding protein; DNA Mutational Analysis; Embryonic growth stage; Fruit flies; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes, Homeobox; Growth hormones; Homeobox; Homeostasis; Hormones; Humanities and Social Sciences; Kinases; letter; Mammals; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; multidisciplinary; Physical growth; Pituitary (anterior); Pituitary Gland - physiology; Promoter Regions, Genetic; Proteins; Rats; Regulatory proteins; Regulatory Sequences, Nucleic Acid; Science; Science (multidisciplinary); Segmentation; Transcription; Transcription Factors - physiology; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Yeasts
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/345829a0

HOMEODOMAIN proteins 1,2 function in determination of mating type in yeast 3 , segmentation in fruit flies 4 and cell-type specific gene expression in mammals 5 . In Drosophila , expression of homeobox genes is controlled by cell-autonomous interactions between regulatory proteins and environmental clues 6–8 . Similar controls may operate during mammalian limb development 9,10 and frog embryogenesis 11,12 . But, the exact way in which expression of homeodomain proteins is regulated in these systems is not clear and requires biochemical analysis of homeobox gene transcription. We now describe such an analysis of the GHF1 gene, which encodes a mammalian homeodomain protein specifying expression of the growth hormone (GH) gene in anterior pituitary somatotrophs 13–15 . GHF1 is transcribed in a highly restricted manner and the presence of GHF1 protein is correlated both temporally and spatially with activation of the GH gene during pituitary development 16 . Analysis of the GHF1 promoter indicates that transcription is also controlled by cell-autonomous interactions involving positive autoregulation by GHF1, and environmental cues that modulate the intracellular level of cyclic AMP and thereby the activity of cAMP response element binding protein (CREB) 17 , a ubiquitous transactivator that binds to the GHF1 promoter.