TY  - JOUR
AU  - Limonciel, Alice
AU  - Moenks, Konrad
AU  - Stanzel, Sven
AU  - Truisi, Germaine L
AU  - Parmentier, Céline
AU  - Aschauer, Lydia
AU  - Wilmes, Anja
AU  - Richert, Lysiane
AU  - Hewitt, Philip
AU  - Mueller, Stefan O
AU  - Lukas, Arno
AU  - Kopp-Schneider, Annette
AU  - Leonard, Martin O
AU  - Jennings, Paul
TI  - Transcriptomics hit the target: Monitoring of ligand-activated and stress response pathways for chemical testing.
JO  - Toxicology in vitro
VL  - 30
IS  - 1 Pt A
SN  - 0887-2333
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2017-03040
SP  - 7 - 18
PY  - 2015
AB  - 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.
KW  - Hazardous Substances (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25596134
DO  - DOI:10.1016/j.tiv.2014.12.011
UR  - https://inrepo02.dkfz.de/record/127014
ER  -