Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

Dongseok Choi, Binoy Appukuttan, Sierra J. Binek, Stephen R. Planck, J. Timothy Stout, James T. Rosenbaum, Justine R. Smith

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p<0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalJournal of Ocular Biology, Diseases, and Informatics
Volume1
Issue number1
DOIs
StatePublished - 2008

Keywords

  • Choroid
  • Endothelial cell
  • Retina
  • cis-Regulatory module
  • cis-Regulatory motif

ASJC Scopus subject areas

  • Ophthalmology
  • Genetics

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