Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm
| Autor: | Matthew C. Pahl, Robert Erdman, Helena Kuivaniemi, John H. Lillvis, James R. Elmore, Gerard Tromp |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | International Journal of Molecular Sciences, Vol 16, Iss 5, Pp 11229-11258 (2015) |
| Druh dokumentu: | article |
| ISSN: | 1422-0067 16051122 |
| DOI: | 10.3390/ijms160511229 |
| Popis: | We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human AAA tissue compared to non-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide chromatin immunoprecipitation. Transcription factor binding was enriched in 4760 distinct genes (FDR < 0.05), of which 713 were differentially expressed in AAA. Functional classification using Gene Ontology (GO), KEGG, and Network Analysis revealed enrichment in several biological processes including “leukocyte migration” (FDR = 3.09 × 10−05) and “intracellular protein kinase cascade” (FDR = 6.48 × 10−05). In the control aorta, the most significant GO categories differed from those in the AAA samples and included “cytoskeleton organization” (FDR = 1.24 × 10−06) and “small GTPase mediated signal transduction” (FDR = 1.24 × 10−06). Genes up-regulated in AAA tissue showed a highly significant enrichment for GO categories “leukocyte migration” (FDR = 1.62 × 10−11), “activation of immune response” (FDR = 8.44 × 10−11), “T cell activation” (FDR = 4.14 × 10−10) and “regulation of lymphocyte activation” (FDR = 2.45 × 10−09), whereas the down-regulated genes were enriched in GO categories “cytoskeleton organization” (FDR = 7.84 × 10−05), “muscle cell development” (FDR = 1.00 × 10−04), and “organ morphogenesis” (FDR = 3.00 × 10−04). Quantitative PCR assays confirmed a sub-set of the transcription factor binding sites including those in MTMR11, DUSP10, ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|