title: Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm.
abstract: 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.
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. mcp3bp@virginia.edu.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pahl
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. rerdman@geisinger.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Erdman
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. shkuivaniemi@geisinger.edu.|Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA. shkuivaniemi@geisinger.edu.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.affiliation: Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48202, USA. johnlillvis@gmail.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Lillvis
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA. jelmore@geisinger.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Elmore
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. gctromp@geisinger.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000473:pathology*; D001665:Binding Sites; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C512897:ELF1 protein, human; C494069:ETS2 protein, human; D009687:Nuclear Proteins; D050787:Proto-Oncogene Protein c-ets-2; C493728:RUNX1 protein, human; D050799:STAT5 Transcription Factor; D014157:Transcription Factors
keywords: KEGG pathway; aneurysm; aorta; chromatin immunoprecipitation; gene expression; gene ontology; genes; network; transcription factor