In Silico Search for Nuclear Receptor Target Genes

Nuclear receptors form a superfamily of proteins that function as ligand-activated transcription factors. One of the authors has pointed out that pathways and networks formed by the nuclear receptors, their ligands, target genes of the nuclear receptors, and their product proteins plays important roles in endocrine regulation, drug and xenobiotic metabolism, and metabolic disorders such as Syndrome X including obesity, type 2 diabetes, hyperlipidemia, hypertension, and atherosclerosis [1]. One of the challenging themes in the study of this field is identification of target genes of the nuclear receptors. This problem is mostly approached from experiment, and only few pilot studies that were ended with many false positive predictions had been carried out. We have started to challenge this problem by focusing our attention on the so called orphan receptors. Orphan receptors are mediators of glucose and lipid metabolism, and are plays pivotal roles in metabolic disorders [2]. Our presentation reports our preliminary work on peroxisome proliferator-activated receptor (PPAR), Liver X receptor (LXR), and hepatocyte nuclear factor 4 alpha (HNF4-alpha). Among these nuclear receptors PPAR (alpha, beta/delta, gamma) are been intensively studied in relation to obesity and diabetes.