Sequencing of the human X chromosome has revealed the existence of many genes that have a unique expression pattern; they are usually expressed in the testis and aberrantly expressed in proliferative tissue, such as cancer. This project proposes to study one family of these genes, the X-antigen gene family (XAGE) whose functions are completely uncharacterized. The overarching goal of this project is to discover the biochemical function of XAGE proteins and to determine the molecular processes that drive their expression. Consistent with Fisk University’s mission to provide students with every tool they need to emerge as future scholars and leaders, this research program will provide Fisk undergraduates with the hands-on opportunity to obtain interdisciplinary scientific knowledge as well as the technical and problem-solving skills that they need to successfully transition to post-undergraduate education and a career in the sciences. In addition to providing faculty mentored research in the investigatos's own laboratory, some of these research concepts and their applications will be introduced in a course-associated laboratory. This project focuses on identifying the underlying mechanisms that cause certain genes on the X chromosome to be expressed only in certain cells at certain times, an area of research that due to its wide scope, is particularly appealing to undergraduate students interested in biological science.
X-antigen genes are located on the X-chromosome and considered to be cancer-testis antigens due to their expression in testis and aberrant expression in proliferative cells. These genes have recently evolved, and their biochemical function and mechanisms regulating either expression is entirely unknown. Using a combination of biochemical and genetic approaches such as tandem affinity IP-Mass Spectrometry and RNA-Sequencing the investogator will determine the biochemical functions of XAGE proteins and those signaling pathways that are perturbed upon aberrant expression. To determine the transcriptional networks and epigenetic mechanisms that lead to this unique expression pattern of XAGE genes, the investigator will perform bioinformatics analysis of methylome sequencing data and promoter elements and then using wet-lab experiments determine the transcription factors that bind to XAGE gene promoters to drive expression. The research will also discover which cis-acting elements, such as enhancers, regulate XAGE expression using Pro-Seq to compare chromatin accessibility in cells expressing XAGE genes versus those that do not. The proposed research will determine whether XAGEs have evolved to provide cells a proliferative or survival advantage and if so, what mechanisms drive their expression.
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.
