Several new transcription factors were discovered to regulate gene expression in the context of endometriosis. A team from the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine conducted an analysis of the proteins that initiate gene expression and found that some of these transcription factors are associated with endometriosis. Regulating these transcription factors may be of interest to further understand the pathogenesis of endometriosis or to develop new therapeutic options.
“Gene expression is under precise regulation by specific transcription factors,” explained Huan Yang, MD, PhD, lead author on the paper, “Integrative Analysis Reveals Regulatory Programs in Endometriosis,” which was published in the journal Reproductive Sciences. “To understand the molecular mechanisms of endometriosis, it is important to identify the regulatory programs underlying this disease.” While other groups have identified that gene expression is altered in endometriosis, Dr. Yang’s group was the first to systematically look at transcription factors to create an integrated regulatory network to explain endometriosis.
As part of this undertaking, Dr. Yang and colleagues at universities in Beijing and Dartmouth looked at the Gene Expression Omnibus database to find genes associated with endometriosis. Two datasets were compiled, and they were analyzed for up- and down-regulated genes in endometriosis. Both sets contained slightly more down-regulated genes than up-regulated ones. When accounting for overlap between sets, there were 701 up-regulated genes and 1090 down-regulated genes. Up-regulated genes were related to defense and immunity proteins, while down-regulated genes were related to structural components of cells.
Putting these genes into a model of regulation, the researchers found that 26 transcription factors regulated 30 important genes, indicating overlap between genes and their regulating transcription factors. Surprisingly, the expression level of the transcription factors themselves were not any different between endometriosis and normal conditions, only their level of regulation of other genes. The most highly associated gene was RUNX1, which encodes for a transcription factor implicated in blood cell production.
“Although the functional relevance of several transcription factors remains unclear, our analysis provides a useful tool to generate new biological insights about transcriptional regulation that may not be acquired directly from gene expression data,” stated Dr. Yang. Identifying transcription factors that differentially regulate genes in endometriosis provides targets for future treatment interventions.