Transcriptomics hit the target: Monitoring of ligand-activated and stress response pathways for chemical testing

Alice Limonciel, Konrad Moenks, Sven Stanzel, Germaine L Truisi, Céline Parmentier, Lydia Aschauer, Anja Wilmes, Lysiane Richert, Philip Hewitt, Stefan O Mueller, Arno Lukas, Annette Kopp-Schneider, Martin O Leonard, Paul Jennings

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

High content omic methods provide a deep insight into cellular events occurring upon chemical exposure of a cell population or tissue. However, this improvement in analytic precision is not yet matched by a thorough understanding of molecular mechanisms that would allow an optimal interpretation of these biological changes. For transcriptomics (TCX), one type of molecular effects that can be assessed already is the modulation of the transcriptional activity of a transcription factor (TF). As more ChIP-seq datasets reporting genes specifically bound by a TF become publicly available for mining, the generation of target gene lists of TFs of toxicological relevance becomes possible, based on actual protein-DNA interaction and modulation of gene expression. In this study, we generated target gene signatures for Nrf2, ATF4, XBP1, p53, HIF1a, AhR and PPAR gamma and tracked TF modulation in a large collection of in vitro TCX datasets from renal and hepatic cell models exposed to clinical nephro- and hepato-toxins. The result is a global monitoring of TF modulation with great promise as a mechanistically based tool for chemical hazard identification.

Original languageEnglish
Pages (from-to)7-18
Number of pages12
JournalToxicology in Vitro
Volume30
Issue number1 Pt A
DOIs
Publication statusPublished - 25 Dec 2015
Externally publishedYes

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Keywords

  • Animals
  • Cell Line
  • Chromatin Immunoprecipitation
  • Databases, Factual
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hazardous Substances
  • Humans
  • Ligands
  • Oligonucleotide Array Sequence Analysis
  • Sequence Analysis, DNA
  • Software
  • Stress, Physiological
  • Transcription Factors
  • Transcriptome
  • Journal Article
  • Research Support, Non-U.S. Gov't

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