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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 10, 2012 |
| Title |
Xenobiotics and loss of cell adhesion drives distinct transcriptional outcomes by Aryl hydrocarbon Receptor (AhR) signaling. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The Aryl hydrocarbon Receptor (AhR) is a signal regulated transcription factor, which is canonically activated by the direct binding of xenobiotics. In addition, switching cells from adherent to suspension culture also activates the AhR, representing a non-xenobiotic, physiological activation of AhR signaling. Here, we show that the AhR is recruited to target gene enhancers in both ligand (YH439) treated and suspension cells, suggesting a common mechanism of target gene induction between these two routes of AhR activation. However, gene expression profiles critically differ between xenobiotic and suspension activated AhR signaling. Por, and Cldnd1 were regulated predominately by ligand treatments, while in contrast, ApoER2 and Ganc were regulated predominately by the suspension condition. Classic xenobiotic metabolizing AhR targets such as Cyp1a1, Cyp1b1, and Nqo1 were regulated by both ligand and suspension conditions. Temporal expression patterns of AhR target genes were also found to vary, with examples of transient activation, transient repression, or sustained alterations in expression. Furthermore, sequence analysis coupled with ChIP assays and reporter gene analysis identified a functional XRE (xenobiotic response element) within the mouse Tiparp gene that features a concatemer of 4 XRE cores (GCGTG) residing in the first intron ~1.2kb downstream of the Tiparp transcription start site. Our data suggest that this XRE concatemer site concurrently regulates the expression of both Tiparp gene and its cis anti-sense non-coding RNA following ligand or suspension induced AhR activation. This work lends novel insights into how AhR signaling drives different transcriptional programs via the ligand versus suspension modes of activation.
Reference: Murray IA et al. (2005) Evidence that ligand binding is a key determinant of Ah receptor-mediated transcriptional activity. Arch Biochem Biophys 442(1):59-71.
Reference: Monk SA et al. (2001) Transient expression of CYP1A1 in rat epithelial cells cultured in suspension. Arch Biochem Biophys 393(1):154-162.
Reference: Chua SW et atl. (2006) A novel normalization method for effective removal of systematic variation in microarray data. Nucleic acids research 34(5):e38.
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| Overall design |
18 microarray samples consisting of AhR null and reconstituted hepatocytes subjected to 10μM YH439, 0.1% DMSO carrier control or grown in suspension culture for 8 hours in 3 biologial replicates.
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| Contributor(s) |
Hao N, Lee KL, Furness SG, Poellinger L, Whitelaw ML |
| Citation(s) |
22936816 |
| Submission date |
Apr 10, 2012 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Kian Leong LEE |
| E-mail(s) |
kianleong.lee@duke-nus.edu.sg
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| Phone |
+(65) 6601 3685
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| Organization name |
National University of Singapore (NUS)
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| Department |
Duke-NUS Medical School
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| Lab |
Cancer & Stem Cell Biology Program (CSCB)
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| Street address |
#07-21, 8 College Road
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| City |
Singapore |
| State/province |
Singapore |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (18)
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| GSM912158 |
AhR null hepatocytes 0.1% DMSO control replicate 1 |
| GSM912159 |
AhR null hepatocytes 0.1% DMSO control replicate 2 |
| GSM912160 |
AhR null hepatocytes 0.1% DMSO control replicate 3 |
| GSM912161 |
AhR null hepatocytes 10μM YH439 replicate 1 |
| GSM912162 |
AhR null hepatocytes 10μM YH439 replicate 2 |
| GSM912163 |
AhR null hepatocytes 10μM YH439 replicate 3 |
| GSM912164 |
AhR null hepatocytes suspension culture replicate 1 |
| GSM912165 |
AhR null hepatocytes suspension culture replicate 2 |
| GSM912166 |
AhR null hepatocytes suspension culture replicate 3 |
| GSM912167 |
AhR reconstituted hepatocytes 0.1% DMSO control replicate 1 |
| GSM912168 |
AhR reconstituted hepatocytes 0.1% DMSO control replicate 2 |
| GSM912169 |
AhR reconstituted hepatocytes 0.1% DMSO control replicate 3 |
| GSM912170 |
AhR reconstituted hepatocytes 10μM YH439 replicate 1 |
| GSM912171 |
AhR reconstituted hepatocytes 10μM YH439 replicate 2 |
| GSM912172 |
AhR reconstituted hepatocytes 10μM YH439 replicate 3 |
| GSM912173 |
AhR reconstituted hepatocytes suspension culture replicate 1 |
| GSM912174 |
AhR reconstituted hepatocytes suspension culture replicate 2 |
| GSM912175 |
AhR reconstituted hepatocytes suspension culture replicate 3 |
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| Relations |
| BioProject |
PRJNA158421 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE37144_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE37144_non_normalized.txt.gz |
5.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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