The Upstream Transcriptional Regulation of the COPD-linked DSP Gene.
Brown, Lucas B.
- Chronic obstructive pulmonary disorder (COPD) is a disease that affects millions of people around the world. There are many factors that can lead to the development of the disease, including certain genetic risk factors. In this study, the upstream regulation of the COPD-linked gene DSP is investigated in an attempt to understand how the gene feeds into the pathology of the disease. A possible ... read moreassociation with the Yap1 transcription factor induced by changes in the stiffness of the matrix was explored. 16HBE cells were grown on plastic and collagen-coated plates that mimicked the extracellular matrix, and no increase in YAP1 expression was observed. Further knockdown experiments with YAP1 did not reveal a strong relationship to DSP expression. The rs2076295 SNP was also investigated, having been linked to lower expression of DSP. A reporter plasmid containing the SNP region upstream of the DSP promoter controlling expression of luciferase was constructed and used to confirm that the risk allele of the SNP region resulted in lower expression levels of DSP in 16HBE cells. The metagenomics tool DeepSEA was used to explore and screen new transcription factor candidates for further experimentation.read less