The challenge of modeling nuclear receptor regulatory networks in mammalian cells.
Nuclear receptors are a major component of signal transduction in animals. They mediate the regulatory activities of many hormones, nutrients and metabolites on the homeostasis and physiology of cells and tissues. It is of high interest to model the corresponding regulatory networks. While molecular and cell biology studies of individual promoters have provided important mechanistic insight, a more complex picture is emerging from genome-wide studies. The regulatory circuitry of nuclear receptor regulated gene expression networks, and their response to cellular signaling, appear highly dynamic, and involve long as well as short range chromatin interactions. We review how progress in understanding the kinetics and regulation of cofactor recruitment, and the development of new genomic methods, provide opportunities but also a major challenge for modeling nuclear receptor mediated regulatory networks.
Jagannathan
Vidhya
V
Department of Ecology and Evolution, Biophore, University of Lausanne, Lausanne CH-1015, Switzerland.
Robinson-Rechavi
Marc
M
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019281:Dimerization; D057890:Epigenomics; D005260:Female; D015870:Gene Expression; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D002843:Chromatin; D018160:Receptors, Cytoplasmic and Nuclear