Published Online
on October 19, 2009

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Original Article

Binding Sites for Ets Family of Transcription Factors Dominate the Promoter Regions of Differentially Expressed Genes in Abdominal Aortic Aneurysms

Jennifer Nischan¹; Zoran Gatalica²; Mindee Curtis²; Guy M. Lenk¹; Gerard Tromp³ and Helena Kuivaniemi^1,4

¹ Wayne State University School of Medicine, Detroit, MI;
² Creighton University School of Medicine, Omaha, NE;
³ Wayne State University School of Medicine

^* Corresponding author; email: shkuivaniemi{at}geisinger.edu

Background—Previously, we identified 3,274 distinct differentially expressed genes in abdominal aortic aneurysm (AAA) tissue compared to non-aneurysmal controls. As transcriptional control is responsible for these expression changes, we sought to find common transcriptional elements in the promoter regions of the differentially expressed genes.

Methods and Results—We analyzed the up- and downregulated gene sets with Whole Genome rVISTA to determine the transcription factor binding sites (TFBSs) overrepresented in the 5 kb promoter regions of the 3,274 genes. The downregulated gene set yielded 144 TFBSs that were overrepresented in the subset when compared to the entire genome. In contrast, the upregulated gene set yielded only 13 distinct overrepresented TFBSs. Interestingly, as classified by TRANSFAC®, 8 of the 13 transcription factors (TFs) binding to these regions belong to the ETS family. Additionally, NFKB and its subunits p50 and p65 showed enrichment. Immunohistochemical analyses in 10 of the TFs from the upregulated analysis showed 9 to be present in AAA tissue. Based on Gene Ontology analysis of biological process categories of the upregulated target genes of enriched TFs, 10 TFs had enrichment in immune system process among their target genes.

Conclusions—Our genome-wide analysis provides further evidence of ETS and NFKB involvement in AAA. Additionally, our results provide novel insight for future studies aiming to dissect the pathogenesis of AAA and have uncovered potential therapeutic targets for AAA prevention.

Key Words: aneurysm • aorta • genomics • transcription factors