Epigenetic Control of Adipogenesis

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Obesity and health complications related to obesity, including diabetes, impact a significant proportion of the population in the United States, and projections indicate that the number of obese and overweight individuals will continue to rise in the future. The costs of health care due to the physical and psycho-social problems caused by obesity and related complications, coupled with the associated loss of productivity, is staggering. Improving strategies to induce lifestyle changes among the obese and overweight population is a necessary strategy toward alleviating this problem, but this approach should be complemented by continued basic research addressing the physiological processes regulating weight gain and adipose formation. While the reguIaton of adipogenesis by adipogenic transcription factors has been extensive(y examined, epigenetic regulators of adipogenesis have not received as much attention. We provide evidence that ATP-dependent chromatin remodeling enzymes and arginine methyltransferases are critical regulators of adipose formation and propose to investigate the mechanisms of action of these enzymes in adipose formation and function in culture and in vivo. Specifically, we will investigate the functional contributions of the histone arginine methyltransferases Prmt5 and Prmt4 in regulating adipogenic gene expression. Additional effort will be placed on investigating the dynamics of histone arginine methylation during adipose formation and function by examining arginine demethylase enzymes. Modulation of epigenetic regulators of gene expression has already proven clinically useful: understanding how such regulators function potentially may lead to strategies that modulate adipogenesis in a manner that is useful for the treatment of obesity and obesity related disease.