Title: AREA R15 application - The role of CTCF in establishing and maintaining chromatin architecture during M. musculus spermatogenesis With the completion of the Human Genome Project in 2003 and the 1000 Genomes Project in 2012, scientists have gained deep understanding of the genetic variation within the human genome, yet with the recent discovery of the inheritance of acquired states (transgenerational inheritance), our understanding of the way in which traits can be passed from parent to offspring has dramatically changed. Though the study of transgenerational inheritance has recently pushed many exciting new boundaries, fundamental questions remain about the more basic functional roles of underlying epigenetic mechanisms. In order for epigenetic patterns to pass from parent to offspring, epigenetic marks must be established during gametogenesis and transmitted to offspring. One of the most widely studied epigenetic marks is chromatin organization yet despite a recent interest in the specialized chromatin patterning exhibited in mammalian gametes, the functional consequence of these patterns remains unknown. Using a specialized suite of molecular tools unique to our laboratory, the study proposed here will focus on the link between the essential DNA binding factor CTCF and the unique chromatin architecture established during spermatogenesis in M. musculus. In line with the goals of the NIH AREA research grant program, students performing the research funded by this proposal at Rowan University will be directly involved in cutting edge molecular biology research techniques while at the same time working on a hypothesis-driven project which has the potential to significantly affect the way in which we approach epigenetic inheritance. The completion of this research project at Rowan will continue to push forward our mission of addressing paradigm-shifting scientific problems while providing students with the best possible avenue to engage in the latest scientific practices to develop highly-trained contributors to the scientific community.
Despite the long-held understanding that genes encoded in DNA define a large part our identity; non-genetic mechanisms play an important role in the inheritance of some human conditions. Though many of these ?epigenetic? inheritance cases have been studied, research in understanding the underlying mechanisms has just begun. This proposed project aims to understand the mechanisms driving the inheritance of these acquired states by studying the way in which these epigenetic marks are established in sperm.
