IADR Abstract Archives
Computational Analysis of X-chromosome Associated Epigenomics in Sjögren’s Syndrome
Objectives: Sjögren’s syndrome (SS) is a female-predominant autoimmune disease affecting exocrine glands causing dry eyes and mouth. The role of X-chromosome genes in SS pathogenesis has not been fully elucidated. Our objectives were to (I) determine how changes in DNA methylation could influence X-chromosome gene expression in SS patients and (II) determine regulatory relationships between differentially methylated or expressed X-chromosome genes, transcription factors, and genes identified by SS association studies.
Methods: An initial list of candidate susceptibility genes was established from published SS association studies. Independently, using the NCBI GEO2R RNA expression analysis tool, we found X-chromosome genes upregulated ≥1.25-fold in three SS salivary gland datasets. We further identified transcription factors upregulated in the three datasets using the TRRUST database. Next, we determined genes previously reported to be differentially methylated in salivary gland epithelial cells to assess the epigenetic contribution in gene expression. Using the online tools STRING and GeneCodis, we established a molecular interaction network and determined the significance of over-represented SS-related pathways.
Results: Among the 48 upregulated X-chromosome genes identified through our analysis, 22 have been previously shown to escape X-chromosome inactivation. In addition, three genes have been shown to indirectly regulate X-inactive specific transcript (XIST). Five upregulated X-chromosome genes and several transcription factors represented in our molecular network were previously shown to be differentially methylated in SS. We also identified X-chromosomal genes implicated in SS pathogenesis regulated by transcription factors overexpressed and/or differentially methylated in SS salivary glands.
Conclusions: We identified overexpressed X-chromosome genes and transcription factors having a regulatory relationship with previously associated SS genes. Future research is needed to elucidate the role epigenetics plays in the regulation of X-chromosome genes and associated transcription factors in SS pathogenesis.
Methods: An initial list of candidate susceptibility genes was established from published SS association studies. Independently, using the NCBI GEO2R RNA expression analysis tool, we found X-chromosome genes upregulated ≥1.25-fold in three SS salivary gland datasets. We further identified transcription factors upregulated in the three datasets using the TRRUST database. Next, we determined genes previously reported to be differentially methylated in salivary gland epithelial cells to assess the epigenetic contribution in gene expression. Using the online tools STRING and GeneCodis, we established a molecular interaction network and determined the significance of over-represented SS-related pathways.
Results: Among the 48 upregulated X-chromosome genes identified through our analysis, 22 have been previously shown to escape X-chromosome inactivation. In addition, three genes have been shown to indirectly regulate X-inactive specific transcript (XIST). Five upregulated X-chromosome genes and several transcription factors represented in our molecular network were previously shown to be differentially methylated in SS. We also identified X-chromosomal genes implicated in SS pathogenesis regulated by transcription factors overexpressed and/or differentially methylated in SS salivary glands.
Conclusions: We identified overexpressed X-chromosome genes and transcription factors having a regulatory relationship with previously associated SS genes. Future research is needed to elucidate the role epigenetics plays in the regulation of X-chromosome genes and associated transcription factors in SS pathogenesis.