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| Status |
Public on Mar 12, 2019 |
| Title |
Transcriptome comparison between WT and GPS2 liver knockout (LKO) livers and GPS2 NCOR PPARa cistrome and epigenome analysis in livers. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Obesity-associated lipid overload triggers non-alcoholic fatty liver diseases (NAFLD), which in part may be driven by alterations of regulatory transcription networks and hepatocyte-selective epigenomes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR)/ histone deacetylase 3 (HDAC3) complex, is a central component of such networks and accelerates the progression of non-alcoholic steatohepatitis (NASH). In hepatocyte-specific Gps2 knockout mice, loss of GPS2 alleviated the development of diet-induced steatosis and fibrosis and caused activation of lipid catabolic genes. By determining differential cistromes, epigenomes and transcriptomes in wild-type, single and double knockout mice, we identified the lipid-sensing nuclear receptor PPARa as a direct target of GPS2. We also provide evidence that in hepatocytes, unlike in macrophages, GPS2 acts in concert with the NCOR subunit of the corepressor complex. By analyzing the liver transcriptomes of human patients, we found that GPS2 expression positively correlated with the expression of NASH/fibrosis signature genes. Collectively, our data suggest that the GPS2-PPARa partnership in hepatocytes may influence the development of NASH/fibrosis in mice and in humans.
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| Overall design |
Transcriptome signatures of GPS2-regulated genes between WT and LKO livers was assessed through RNA-seq analysis. Epigenomic status of Gps2, Ncor and Smrt LKO vs WT livers was analyzed using histone markers H3K4me3 and/or H3K27ac ChIP-seq. GPS2, NCOR and PPARa cistrome was analyzed in Gps2, Ncor and Ppara WT/KO livers respectively.
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| Contributor(s) |
Liang N, Damdimopoulos A, Treuter E, Fan R |
| Citation(s) |
30975991 |
| Submission date |
Apr 16, 2018 |
| Last update date |
Nov 05, 2019 |
| Contact name |
Rongrong Fan |
| E-mail(s) |
rongrong.fan@ki.se
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| Organization name |
Karolinska Institutet
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| Street address |
Hälsovägen 7c
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| City |
Huddinge |
| ZIP/Postal code |
14152 |
| Country |
Sweden |
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| Platforms (2) |
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| Samples (74)
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| Relations |
| BioProject |
PRJNA450317 |
| SRA |
SRP140448 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113157_RAW.tar |
32.9 Mb |
(http)(custom) |
TAR (of BED) |
| GSE113157_Subread_counts_and_DE_genes_in_GPS2_WT_LKO_liver_RNAseq.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_GPS2_peaks_in_GPS2_WT_LKO_livers.txt.gz |
4.0 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_GPS2_peaks_in_NCOR_WT_LKO_livers.txt.gz |
5.0 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_GPS2_peaks_in_PPARa_WT_KO_livers.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_H3K27ac_peaks_in_NCOR_SMRT_WT_LKO_livers.txt.gz |
7.2 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_H3K4me3_H3K27ac_peaks_in_GPS2_WT_LKO_livers.txt.gz |
8.2 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_NCOR_peaks_in_GPS2_WT_LKO_livers.txt.gz |
7.3 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_NCOR_peaks_in_PPARa_WT_KO_livers.txt.gz |
10.3 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_PPARa_peaks_in_GPS2_WT_LKO_livers.txt.gz |
9.2 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_PPARa_peaks_in_NCOR_WT_LKO_livers.txt.gz |
7.8 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_PPARa_peaks_in_PPARa_WT_KO_livers.txt.gz |
3.4 Mb |
(ftp)(http) |
TXT |
| GSE113157_raw_tag_counts_of_PolII_peaks_in_GPS2_WT_LKO_livers.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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