The function of epigenetic memory in cell fate

Emory University, Atlanta GA

Investigators

Abstract

Within an organism, every different type of cell contains the same set genes, but only a subset of these genes are on. This gives rise to the many different types of cells. Over many years scientists have made a lot of progress on understanding how the packaging of genes into an open or closed formation determines whether the gene will be on or off. This is a fundamental part of biology. However, scientists still have very little understanding of whether the packaging of genes can serve as heritable information from one generation to the next. There is also very little known about the mechanisms through which defects in the packaging of DNA influence the formation of the nervous system and behavior. The microscopic worm C. elegans is the perfect system to address these questions because of the short generation time and simple invariant nervous system. The Katz lab discovered transgenerational defects in sterility and behavior in these worms caused by the misregulation of the packaging of genes. By studying these defects, the Katz lab will address fundamental aspects of biology and behavior with wide ranging implications for many different processes. These experiments are highly complementary to broader impacts. The Katz Lab at Emory University has partnered with a nearby liberal arts college, Oglethorpe University, to establish a Pipeline Course Embedded Undergraduate Research (CURE) curriculum, where biology majors take part in C. elegans research reiteratively throughout the biology major. This culminates in a Capstone Course, where students spend the bulk of their class time over a semester on an original C. elegans research project related to ongoing experiments in the Katz Lab. Data collected throughout the implementation of the program indicate that this original research in the classroom can recapitulate the experience that is typically only found in an apprentice style approach at a major research university. To continue to lower the bar of accessibility to original research at a liberal arts college, the Katz Lab proposes to provide every biology major the opportunity to conduct thesis research performed entirely in the classroom at Oglethorpe University. Using C. elegans, the Katz lab discovered multiple new phenotypes caused by mutations in histone modifying proteins. 1) The transgenerational accumulation of H3K4me2 causes abnormal chemotaxis behavior. This altered behavior can be reversed in adult animals by turning off the inappropriate transcription, suggesting that the behavior defect is not due to a developmental defect, but is instead caused by an ongoing defect in a normally formed nervous system. 2) The transgenerational accumulation of histone H3 acetylation leads to sterility across generations. 3) The transgenerational accumulation of the H3K9me2 results in altered chemotaxis behavior across generations. By studying these novel phenotypes, the Katz lab will uncover how altered chromatin can serve as heritable transgenerational information and how defects in transcription caused by the misregulation of histone methylation can actively alter behavior. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.