REGULATION OF HYPOTHALAMIC EXPRESSION OFTHE PROOPIOMELANOCORTIN GENE BY NUCLEAR RECEPTOR FACTORS

DE SOUSA, FJS; RUBINSTEIN M

San Miguel de Tucumán

Congreso; XLV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

SAIB

The proopiomelanocortin (POMC) gene encodes a prohormone expressed mainly in the pituitary and the arcuate nucleus of the hypothalamus. POMC-derived peptides play important roles in responding to stress and controlling food intake and energy balance. We have identified two enhancers - named nPE1 and nPE2 - that control POMC expression in the mammalian hypothalamus. To identify transcription factors that might control POMCproopiomelanocortin (POMC) gene encodes a prohormone expressed mainly in the pituitary and the arcuate nucleus of the hypothalamus. POMC-derived peptides play important roles in responding to stress and controlling food intake and energy balance. We have identified two enhancers - named nPE1 and nPE2 - that control POMC expression in the mammalian hypothalamus. To identify transcription factors that might control POMCPOMC expression in the mammalian hypothalamus. To identify transcription factors that might control POMCPOMC expression, we performed an one-hybrid screening with nPE2 as bait and identified factors of the nuclear receptor superfamily that can bind to an element in nPE2 that follows the consensus binding site for these factors. In addition, this element is conserved in all mammals and is present within a crucial region for nPE2 enhancer activity. Since the factors we identified by one-hybrid screening are not co-expressed with POMC in the brain, we sought to find other factors based on the literature. One candidate is oestrogen receptorPOMC in the brain, we sought to find other factors based on the literature. One candidate is oestrogen receptor a (ERa) which is known to be involved in the control of POMC(ERa) which is known to be involved in the control of POMC expression and energy balance, and is widely expressed in the brain. By immunohistochemistry using a transgenic mouse model, we found that around 30% of POMC-EGFP neurons co-express ERa, indicating that this transcription factor is a strong candidate for regulating the expression of the POMC gene. Further functional studies are needed to corroborate this hypothesis.a, indicating that this transcription factor is a strong candidate for regulating the expression of the POMC gene. Further functional studies are needed to corroborate this hypothesis.POMC gene. Further functional studies are needed to corroborate this hypothesis.