Regulation of hypothalamic expression of the proopiomelanocortin gene by nuclear receptor factors

DE SOUZA FS; RUBINSTEIN M

Tucumán

Congreso; Annual Meeting Argentine Society for Biochemistry and Molecular Biology (SAIB) XLV; 2009

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 POMC expression, we performed an one-hybrid screening with nPE2 as bait and identified factors of the nuclear receptor superfamily that can bind to a site 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 receptor a (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.