Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting
The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-of-function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a hig...
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2005
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02707306_v25_n8_p3076_DeSouza http://hdl.handle.net/20.500.12110/paper_02707306_v25_n8_p3076_DeSouza |
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paper:paper_02707306_v25_n8_p3076_DeSouza2023-06-08T15:24:56Z Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting proopiomelanocortin animal tissue article brain controlled study DNA footprinting DNA polymorphism gene deletion genetic analysis hypophysis hypothalamus mouse nonhuman phylogeny priority journal protein expression protein localization reporter gene transgenic mouse Animals Arcuate Nucleus Base Sequence Conserved Sequence DNA Mutational Analysis Enhancer Elements (Genetics) Gene Expression Regulation Genes, Reporter Green Fluorescent Proteins Humans Mice Mice, Transgenic Molecular Sequence Data Neurons Obesity Phylogeny Pituitary Gland, Anterior Polymorphism, Genetic Pro-Opiomelanocortin Sequence Deletion Mammalia Mus musculus The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-of-function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity. Copyright © 2005, American Society for Microbiology. All Rights Reserved. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02707306_v25_n8_p3076_DeSouza http://hdl.handle.net/20.500.12110/paper_02707306_v25_n8_p3076_DeSouza |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
proopiomelanocortin animal tissue article brain controlled study DNA footprinting DNA polymorphism gene deletion genetic analysis hypophysis hypothalamus mouse nonhuman phylogeny priority journal protein expression protein localization reporter gene transgenic mouse Animals Arcuate Nucleus Base Sequence Conserved Sequence DNA Mutational Analysis Enhancer Elements (Genetics) Gene Expression Regulation Genes, Reporter Green Fluorescent Proteins Humans Mice Mice, Transgenic Molecular Sequence Data Neurons Obesity Phylogeny Pituitary Gland, Anterior Polymorphism, Genetic Pro-Opiomelanocortin Sequence Deletion Mammalia Mus musculus |
| spellingShingle |
proopiomelanocortin animal tissue article brain controlled study DNA footprinting DNA polymorphism gene deletion genetic analysis hypophysis hypothalamus mouse nonhuman phylogeny priority journal protein expression protein localization reporter gene transgenic mouse Animals Arcuate Nucleus Base Sequence Conserved Sequence DNA Mutational Analysis Enhancer Elements (Genetics) Gene Expression Regulation Genes, Reporter Green Fluorescent Proteins Humans Mice Mice, Transgenic Molecular Sequence Data Neurons Obesity Phylogeny Pituitary Gland, Anterior Polymorphism, Genetic Pro-Opiomelanocortin Sequence Deletion Mammalia Mus musculus Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| topic_facet |
proopiomelanocortin animal tissue article brain controlled study DNA footprinting DNA polymorphism gene deletion genetic analysis hypophysis hypothalamus mouse nonhuman phylogeny priority journal protein expression protein localization reporter gene transgenic mouse Animals Arcuate Nucleus Base Sequence Conserved Sequence DNA Mutational Analysis Enhancer Elements (Genetics) Gene Expression Regulation Genes, Reporter Green Fluorescent Proteins Humans Mice Mice, Transgenic Molecular Sequence Data Neurons Obesity Phylogeny Pituitary Gland, Anterior Polymorphism, Genetic Pro-Opiomelanocortin Sequence Deletion Mammalia Mus musculus |
| description |
The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-of-function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity. Copyright © 2005, American Society for Microbiology. All Rights Reserved. |
| title |
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| title_short |
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| title_full |
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| title_fullStr |
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| title_full_unstemmed |
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| title_sort |
identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting |
| publishDate |
2005 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02707306_v25_n8_p3076_DeSouza http://hdl.handle.net/20.500.12110/paper_02707306_v25_n8_p3076_DeSouza |
| _version_ |
1768544684839272448 |