Measuring changes in nuclear receptor binding during fetal and neonatal development using chromatin immunoprecipitation (ChIP)

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The inverse relationship between birth weight and post partum health is one of the most fascinating discoveries in mammalian fetal biology. The principal hypothesis governing this relationship, termed 'fetal programming', is that genetic and/or epigenetic changes underlie alterations in fetal development. Understanding the overall role of nuclear receptors in mediating these developmental events would provide us with a better understanding of the mechanisms controlling fetal development. To date, many published studies have been focused upon the effect of maternal insults (i.e. malnutrition and hypoxemia) on specific target genes and physiological parameters in the fetus and neonate. Although this approach is informative, it fails to address by design the more global role of transcription factors (e.g. nuclear receptors) and epigenetic modifications involved underlying the 'reprogramming' of the fetal genome. Collectively, the equipment requested in this proposal will address this deficiency by facilitating the use chromatin immunoprecitation (ChIP) in tissues to examine the alterations in vivo binding of nuclear receptors to the promoters of their respective target genes. Specifically, with the purchase of an S-4000 Sonicator, and an 8-sample Nanodrop Spectrophotometer, we will have the ability to isolate and measure chromatin changes, respectively, during fetal development. With this unique model, we can examine for the first time the developmental changes in the in vivo interactions of nuclear receptors and epigenetic markers to target promoters, which play an important role in the coordinated control of gene transcription during normal and abnormal fetal development.