ArticleMolecular and cellular biology1992
Identification of DNA elements cooperatively activating proopiomelanocortin gene expression in the pituitary glands of transgenic mice.
Article in Molecular and cellular biology, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 64 citations in OpenAlex.
- OCT4 modulates Pomc gene transcription by interfering with specific corticotroph transcription factors.Journal of endocrinological investigation · 2026Article
- Molecular and functional genetics of the proopiomelanocortin gene, food intake regulation and obesity.FEBS letters · 2017Review
- Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling.The Journal of cell biology · 2016Article
- A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease.Nature medicine · 2015Article
- Enhancer turnover and conserved regulatory function in vertebrate evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Article
- Molecular anatomy of the gut-brain axis revealed with transgenic technologies: implications in metabolic research.Frontiers in neuroscience · 2013Article
- A pituitary-specific enhancer of the POMC gene with preferential activity in corticotrope cells.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Developmental dependence on NurRE and EboxNeuro for expression of pituitary proopiomelanocortin.Molecular endocrinology (Baltimore, Md.) · 2008Article
- Nasal administration of osteopontin peptide mimetics confers neuroprotection in stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2008Article
- Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting.Molecular and cellular biology · 2005Article
- Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland.Molecular and cellular biology · 2005Article
- A transgenic marker for newly born granule cells in dentate gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Retinoic acid prevents experimental Cushing syndrome.The Journal of clinical investigation · 2001Article
- Transgenic and knockout mouse models clarify pituitary development, function and disease.Brain pathology (Zurich, Switzerland) · 2001Review
- Authentic cell-specific and developmentally regulated expression of pro-opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1998Article
- Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein.Pituitary · 1998Article
- DNA elements with AT-rich core sequences direct pituitary cell-specific expression of the pro-opiomelanocortin gene in transgenic mice.The Biochemical journal · 1995Article
- Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
- Functional redundancy of the DE-1 and alpha A-CRYBP1 regulatory sites of the mouse alpha A-crystallin promoter.Nucleic acids research · 1993Article
- Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene.The EMBO journal · 1993Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The proopiomelanocortin (POMC) gene is highly expressed in adult mouse pituitary anterior lobe corticotrophs and intermediate lobe melanotrophs. To identify the DNA elements important for this tissue-specific expression, we analyzed a series of POMC reporter genes in transgenic mice. A DNA fragment containing rat POMC 5'-flanking sequences from -323 to -34 recapitulated both basal pituitary cell-specific and hormonally stimulated expression in adult mice when fused to a heterologous thymidine kinase promoter. Developmental onset of the reporter gene expression lagged by 1 day but otherwise closely paralleled the normal ontogeny of murine POMC gene expression, including corticotroph activation at embryonic day 14.5 (E14.5) followed by melanotroph activation at E15.5 to E16.5. AtT20 corticotroph nuclear protein extracts interacted with three specific regions of the functional POMC promoter in DNase I protection assays. The positions of these protected sites were -107 to -160 (site 1), -182 to -218 (site 2), and -249 to -281 (site 3). Individual deletions of these footprinted sites did not alter transgene expression; however, the simultaneous deletion of sites 2 and 3 prevented transgene expression in both corticotrophs and melanotrophs. Electrophoretic mobility shift and Southwestern (DNA-protein) assays demonstrated that multiple AtT20 nuclear proteins bound to these footprinted sites. We conclude that the sequences between -323 and -34 of the rat POMC gene promoter are both necessary and sufficient for correct spatial, temporal, and hormonally regulated expression in the pituitary gland. Our data suggest that the three footprinted sites within the promoter are functionally interchangeable and act in combination with promoter elements between -114 and -34. The inability of any reporter gene construction to dissociate basal and hormonally stimulated expression suggests that these DNA elements are involved in both of these two characteristics of POMC gene expression in vivo.
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