Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting

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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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Autor principal: De Souza, F.S.J
Otros Autores: Santangelo, Andrea Mariana, Bumaschny, V., Avale, M.E, Smart, J.L, Low, M.J, Rubinstein, M.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2005
Acceso en línea:Registro en Scopus
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Biblioteca Central Dr. Luis F. Leloir (FCEN) de Universidad de Buenos Aires
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024 7 |2 cas  |a proopiomelanocortin, 66796-54-1; enhanced green fluorescent protein; Green Fluorescent Proteins, 147336-22-9; Pro-Opiomelanocortin, 66796-54-1 
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100 1 |a De Souza, F.S.J. 
245 1 0 |a Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting 
260 |c 2005 
270 1 0 |m Rubinstein, M.; INGEBI-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina; email: mrubins@dna.uba.ar 
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506 |2 openaire  |e Política editorial 
520 3 |a 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.  |l eng 
593 |a Inst. Invest. Ing. Genet. Biol. M., CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Vollum Institute, Oregon Health and Science University, Portland, OR, United States 
593 |a Dept. of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States 
593 |a Ctr. Stud. Weight Reg. Assoc. D., Oregon Health and Science University, Portland, OR, United States 
593 |a Centrode Estudios Científicos, Valdivia, Chile 
593 |a INGEBI-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina 
690 1 0 |a PROOPIOMELANOCORTIN 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ARTICLE 
690 1 0 |a BRAIN 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DNA FOOTPRINTING 
690 1 0 |a DNA POLYMORPHISM 
690 1 0 |a GENE DELETION 
690 1 0 |a GENETIC ANALYSIS 
690 1 0 |a HYPOPHYSIS 
690 1 0 |a HYPOTHALAMUS 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PHYLOGENY 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a PROTEIN LOCALIZATION 
690 1 0 |a REPORTER GENE 
690 1 0 |a TRANSGENIC MOUSE 
690 1 0 |a ANIMALS 
690 1 0 |a ARCUATE NUCLEUS 
690 1 0 |a BASE SEQUENCE 
690 1 0 |a CONSERVED SEQUENCE 
690 1 0 |a DNA MUTATIONAL ANALYSIS 
690 1 0 |a ENHANCER ELEMENTS (GENETICS) 
690 1 0 |a GENE EXPRESSION REGULATION 
690 1 0 |a GENES, REPORTER 
690 1 0 |a GREEN FLUORESCENT PROTEINS 
690 1 0 |a HUMANS 
690 1 0 |a MICE 
690 1 0 |a MICE, TRANSGENIC 
690 1 0 |a MOLECULAR SEQUENCE DATA 
690 1 0 |a NEURONS 
690 1 0 |a OBESITY 
690 1 0 |a PHYLOGENY 
690 1 0 |a PITUITARY GLAND, ANTERIOR 
690 1 0 |a POLYMORPHISM, GENETIC 
690 1 0 |a PRO-OPIOMELANOCORTIN 
690 1 0 |a SEQUENCE DELETION 
690 1 0 |a MAMMALIA 
690 1 0 |a MUS MUSCULUS 
700 1 |a Santangelo, Andrea Mariana 
700 1 |a Bumaschny, V. 
700 1 |a Avale, M.E. 
700 1 |a Smart, J.L. 
700 1 |a Low, M.J. 
700 1 |a Rubinstein, M. 
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