Details

Autor(en) / Beteiligte

• Nischan, Jennifer
• Gatalica, Zoran
• Curtis, Mindee
• Lenk, Guy M
• Tromp, Gerard
• Kuivaniemi, Helena

Titel

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

Ist Teil von

• Circulation. Cardiovascular genetics, 2009-12, Vol.2 (6), p.565-572

Ort / Verlag

United States

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Binding Sites for ETS Family of Transcription Factors Dominate the Promoter Regions of Differentially Expressed Genes in Abdominal Aortic Aneurysms Jennifer Nischan, MS ; Zoran Gatalica, MD, DSc ; Mindee Curtis, BS ; Guy M. Lenk, PhD ; Gerard Tromp, PhD and Helena Kuivaniemi, MD, PhD From the Center for Molecular Medicine and Genetics (J.N., G.M.L., G.T., H.K.), and the Departments of Neurology (G.T.) and Surgery (H.K.), Wayne State University School of Medicine, Detroit, Mich; and the Department of Pathology (Z.G., M.C.), Creighton University School of Medicine, Omaha, Nebr. Current affiliations: Department of Human Genetics (G.M.L.), University of Michigan, Ann Arbor; and Weis Center for Research (G.T., H.K.), Geisinger Clinic, Danville, Pa. Correspondence to Helena Kuivaniemi, MD, PhD, FAHA, Weis Center for Research, Geisinger Clinic, 100 N Academy Ave, Danville, PA 17822. E-mail shkuivaniemi{at}geisinger.edu Received December 12, 2008; accepted September 21, 2009. Background— Previously, we identified 3274 distinct differentially expressed genes in abdominal aortic aneurysm (AAA) tissue compared with nonaneurysmal 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 (TF) binding sites overrepresented in the 5-kb promoter regions of the 3274 genes. The downregulated gene set yielded 144 TF binding sites that were overrepresented in the subset when compared with the entire genome. In contrast, the upregulated gene set yielded only 13 distinct overrepresented TF binding sites. Interestingly, as classified by TRANSFAC, 8 of the 13 TFs binding to these regions belong to the ETS family. Additionally, nuclear factor kB and its subunits p50 and p65 showed enrichment. Immunohistochemical analyses of 10 TFs from the upregulated set 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 nuclear factor kB 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   CLINICAL PERSPECTIVE The online-only Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.843854. Home | Subscriptions | Archives | Feedback | Authors | Help | Circulation Journals Home | AHA Journals Home | Search Copyright © 2009 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. var _rsCI="us-lippincott"; var _rsCG="0"; var _rsDN="//secure-us.imrworldwide.com/"; var _rsSE=1; var _rsSM=1.0;