Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm

International Journal of Molecular Sciences

Matthew C. Pahl²  Robert Erdman²  Helena Kuivaniemi²  John H. Lillvis³  James R. Elmore¹  Gerard Tromp² 

[1] Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA; E-Mail:;Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA; E-Mails:;Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48202, USA; E-Mail:

关键词: aneurysm;    aorta;    genes;    transcription factor;    chromatin immunoprecipitation;    gene expression;    gene ontology;    KEGG pathway;    network;   

DOI  :  10.3390/ijms160511229

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.