Artículo

De Souza, F.S.J.; Santangelo, A.M.; Bumaschny, V.; Avale, M.E.; Smart, J.L.; Low, M.J.; Rubinstein, M. "Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting" (2005) Molecular and Cellular Biology. 25(8):3076-3086
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Abstract:

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.

Registro:

Documento: Artículo
Título:Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting
Autor:De Souza, F.S.J.; Santangelo, A.M.; Bumaschny, V.; Avale, M.E.; Smart, J.L.; Low, M.J.; Rubinstein, M.
Filiación:Inst. Invest. Ing. Genet. Biol. M., CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina
Vollum Institute, Oregon Health and Science University, Portland, OR, United States
Dept. of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States
Ctr. Stud. Weight Reg. Assoc. D., Oregon Health and Science University, Portland, OR, United States
Centrode Estudios Científicos, Valdivia, Chile
INGEBI-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2005
Volumen:25
Número:8
Página de inicio:3076
Página de fin:3086
DOI: http://dx.doi.org/10.1128/MCB.25.8.3076-3086.2005
Título revista:Molecular and Cellular Biology
Título revista abreviado:Mol. Cell. Biol.
ISSN:02707306
CODEN:MCEBD
CAS:proopiomelanocortin, 66796-54-1; enhanced green fluorescent protein; Green Fluorescent Proteins, 147336-22-9; Pro-Opiomelanocortin, 66796-54-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02707306_v25_n8_p3076_DeSouza

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Citas:

---------- APA ----------
De Souza, F.S.J., Santangelo, A.M., Bumaschny, V., Avale, M.E., Smart, J.L., Low, M.J. & Rubinstein, M. (2005) . Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting. Molecular and Cellular Biology, 25(8), 3076-3086.
http://dx.doi.org/10.1128/MCB.25.8.3076-3086.2005
---------- CHICAGO ----------
De Souza, F.S.J., Santangelo, A.M., Bumaschny, V., Avale, M.E., Smart, J.L., Low, M.J., et al. "Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting" . Molecular and Cellular Biology 25, no. 8 (2005) : 3076-3086.
http://dx.doi.org/10.1128/MCB.25.8.3076-3086.2005
---------- MLA ----------
De Souza, F.S.J., Santangelo, A.M., Bumaschny, V., Avale, M.E., Smart, J.L., Low, M.J., et al. "Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting" . Molecular and Cellular Biology, vol. 25, no. 8, 2005, pp. 3076-3086.
http://dx.doi.org/10.1128/MCB.25.8.3076-3086.2005
---------- VANCOUVER ----------
De Souza, F.S.J., Santangelo, A.M., Bumaschny, V., Avale, M.E., Smart, J.L., Low, M.J., et al. Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting. Mol. Cell. Biol. 2005;25(8):3076-3086.
http://dx.doi.org/10.1128/MCB.25.8.3076-3086.2005