Deciphering Transcriptional Regulation Relevant to Eating Behavior

The Agouti Related Protein (AgRP), Neuropeptide Y (NPY), Cocaine and Amphetamine-Regulated Transcript (CART), and Proopiomelanocortin hormone (POMC) are four essential neuropeptides that play an import role in regulation of food intake and energy homeostasis in mammals. Each of the two pairs of neuropeptides, AgRP / NPY and CART / POMC, are co-expressed in distinctly separate neurons in the hypothalamus. The four neuropeptides are also expressed widely in peripheral tissues with the adrenal gland being the major site of expression except in the case of NPY that is expressed predominantly in the prostate. There is abundant information regarding the physiological roles of these genes but there is limited information regarding their transcriptional regulation in the brain and the periphery. We employed multiple in silico methods from genome-wide applications and genomic sequence from promoter regions to predict common and unique regulatory patterns of transcription for these genes. hCART and hPOMC are phylogenetically closely related in terms of the common transcription factors (TFs) that were predicted for the two promoters, whereas hAgRP is a distant relative to hNPY. We also identified short regions (20 nucleotides or less) in the promoters of pairs of these genes that were 100% identical and are candidate TF binding sites. These studies provide a paradigm for analogous applications to other co-regulated genes and could lead to the identification of functional promoter targets for interventional therapies.