Master of Science in Bioinformatics (MSBI)
Sequence Paired Site (SPS), Notch1, Notch Transcription Complex (NTC), Notch Response Element (NRE)
The completion of the Human Genome Project in 2003 made it possible to leverage the power of computers to quicken biological discoveries. The human genome contains rich information relevant to the proper functions of cells that is computationally arduous and costly to investigate in a laboratory setting. Specifically, gene expression levels in cells can be impacted when functionally relevant motifs in the DNA are mutated preventing proper transcription factor binding. To study the consequences of such mutations, it is necessary to first identify such functionally relevant regions of the genome using computational approaches. A signaling pathway that is of particular interest and important to cell differentiation, proliferation, apoptosis, and homeostasis is the Notch1 pathway. Mutations in the Notch1 pathway can lead to developmental defects, early embryonic death, and various forms of cancers such as T-cell lymphoblastic leukemia. The transcription machinery required for the expression of some Notch1 target genes include the binding of the transcription factor CSL to Notch response elements (NRE) located in the promoter region of Notch1 target genes and the formation of a transcription complex. Sequence paired sites (SPSs) are a pair of NREs with a varying spacer region that allow for the transcription factor CBF1 to bind to the cognate DNA which aids in the formation of a dimer regulating activation of downstream Notch1 target genes. Prior research has shown that mutations within the SPS have been found to significantly affect the activation of Hes1. This project will introduce a novel bioinformatics tool used to find potential SPSs in the genome and identify downstream genes for further study.
Sundar, Punit, "Conservation and Prevalence of Sequence Paired Sites in Humans" (2022). Master's Projects. 1095.