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| Status |
Public on Jan 18, 2014 |
| Title |
T-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
β-catenin signaling can be both a physiological and an oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20 to 40% of hepatocellular carcinomas with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by Tcf4 and β-catenin, their transcriptome and their metabolome. We find that Tcf4 DNA-bindings depend on β-catenin. Tcf4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf4 on Hnf4-responsive elements. β-catenin, Tcf4 and Hnf4α interact, dictating β-catenin transcription which is antagonistic to that elicited by Hnf4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. We conclude that β-catenin patterns the zonal liver together with Tcf4, Hnf4α and xenobiotic nuclear receptors. This network represses lipid metabolism, and exacerbates glutamine, drug and bile metabolism, mirroring hepatocellular carcinomas with β-catenin mutational activation.
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| Overall design |
In vivo liver samples in 4 conditions: Betacat activated (WCE, Tcf4 chipseq, Betacat chipseq, mRNAseq with 2 replicates), Betacat null (WCE, Tcf4 chipseq, mRNAseq with 2 replicates), Betacat control (mRNAseq with 2 replicates), Wild type (mRNAseq with 2 replicates)
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| Contributor(s) |
Gougelet A, Torre C, Veber P, Sartor C, Bachelot L, Denechaud P, Godard C, Moldes M, Burnol A, Dubuquoy C, Terris B, Guillonneau F, Ye T, Schwarz M, Braeuning A, Perret C, Colnot S |
| Citation(s) |
24214913 |
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| Submission date |
Jan 19, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Philippe Veber |
| E-mail(s) |
philippe.veber@univ-lyon1.fr
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| Organization name |
CNRS
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| Lab |
Laboratoire de Biométrie et Biologie Évolutive.
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| Street address |
16 rue Raphael Dubois
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| City |
Villeurbanne |
| ZIP/Postal code |
69622 |
| Country |
France |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (13)
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| Relations |
| SRA |
SRP010458 |
| BioProject |
PRJNA150641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35213_AK-BK.tsv.gz |
1.4 Mb |
(ftp)(http) |
TSV |
| GSE35213_AK-TAM.tsv.gz |
1.4 Mb |
(ftp)(http) |
TSV |
| GSE35213_AK-WT.tsv.gz |
1.4 Mb |
(ftp)(http) |
TSV |
| GSE35213_BK-TAM.tsv.gz |
1.2 Mb |
(ftp)(http) |
TSV |
| GSE35213_BK-WT.tsv.gz |
1.3 Mb |
(ftp)(http) |
TSV |
| GSE35213_RAW.tar |
3.5 Mb |
(http)(custom) |
TAR (of BED) |
| GSE35213_TAM-WT.tsv.gz |
1.2 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
| Raw data are available in SRA |
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