Spatial changes in gene organization during adipogenesis

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DESCRIPTION (provided by applicant): Obesity and health complications related to obesity, including diabetes, impact a significant proportion of the population in the U.S., 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, are staggering. While it is necessary to improve strategies that will result in lifestyle changes among the obese and overweight population, basic research toward understanding the physiological processes regulating weight gain must be continued. Considerable effort has been placed on identifying genes that are turned on during the formation of adipose tissue, investigating their function, and determining the mechanisms by which the expression of these genes are regulated. Identification of molecules that contribute to adipogenesis will likely continue to lead to the development of strategies to modulate adipogenesis in a manner that is useful for the treatment of obesity and obesity related disease. However, recently developed methodologies have led to an emerging field of research that does not simply focus on the regulation of individual genes but instead permits analysis of the three-dimensional structure of genes involved in any biological process of interest. Our initial studies reveal that shortly after the onset of adipogenic differentiation, genes that will be expressed during adipogenesis are physically associated with each other in three-dimensional space despite the fact that they are located on different chromosomes and were not in contact prior to differentiation. This gene association, or clustering, is a previously uncharacterized event that occurs during adipogenesis. The PI and the co-PI, who developed the methodologies that led to this discovery, now seek to further characterize gene clustering during adipogenesis, investigate its functional relevance, and identify factors that contribute to or are required for its occurrence. We envision that ultimately our studies and others that are similar in nature will result in the definition of new processes controlling gene expression and cellular differentiation and in the identification of previously unknown molecules that mediate these processes. Furthermore, we propose that such molecules may represent an entirely new class of targets for drug design and screening. Obesity and health complications related to obesity, including diabetes, impact a significant proportion of the population in the U.S. While it is necessary to improve strategies that will result in lifestyle changes among the obese and overweight population, basic research toward understanding the physiological processes regulating weight gain must be continued. We have discovered that genes that will be expressed during the formation of fat cells are physically associated with each other in three-dimensional space despite the fact that they are located on different chromosomes and were not in contact prior to fat cell differentiation. This gene association, or clustering, is a previously uncharacterized event that occurs during adipogenesis. Further characterization of gene clustering may result in the definition of new processes controlling gene expression and cellular differentiation and in the identification of previously unknown molecules that mediate these processes. Such molecules may represent an entirely new class of targets for future therapies.