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| Status |
Public on Feb 23, 2019 |
| Title |
Small Heterodimer Partner and Fibroblast Growth Factor-19 Inhibit Intestinal Npc1l1 Expression and Cholesterol Absorption |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Small Heterodimer Partner (SHP/NR0B2) is an unusual orphan nuclear receptor that does not have a DNA binding domain and acts as a co-repressor for many transcriptional factors, including LRH-1, SREBPs, FOXA1, and AhR, which inhibits expression of its target genes. To explore global intestinal functions of SHP, WT and SHP-KO mice were fed for 6 h after fasting overnight. In SHP-KO mice, 1,707 genes were upregulated, and 1,055 genes downregulated by 2-fold or more compared to WT mice. In GO analysis, intestinal genes upregulated with the highest significance were involved in the transport of ions, lipids, and hormones, and in cholesterol metabolic processes; whereas genes downregulated were involved in the cell cycle, the immune response, and apoptosis. Remarkably, expression of genes important for cholesterol absorption, including Npc1l1, sterol biosynthetic genes, including Hmgcr, and key intestinal bile acid transporters, Asbt and Ost-alpha/beta, was altered in SHP-KO mice compared to WT mice. Overall, in this study, SHP was shown to be a gene-specific transcriptional partner of SREBP-2 to epigenetically inhibit cholesterol-regulating genes, including Npc1l1, in the late-fed state.
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| Overall design |
Intestinal mRNA profiles were generated by deep sequencing, were profiled at the intestine (Jejunum and Ileum) in wild-type (WT) and SHP-KO mice fed for 6 h after fasting overnight.
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| Contributor(s) |
Kim Y, Byun S, Seok S, Guo G, Xu HE, Kemper B, Kim Kemper J |
| Citation(s) |
30521806 |
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| Submission date |
Feb 22, 2019 |
| Last update date |
May 28, 2019 |
| Contact name |
Young-Chae Kim |
| E-mail(s) |
ychaekim@illinois.edu
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| Phone |
217-244-2236
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| Organization name |
University of Illinois at Urbana-Champaign
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| Department |
MIP
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| Lab |
Kemper's lab
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| Street address |
394 Burrill Hall 407 S. Goodwin Ave
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| City |
Urbana |
| State/province |
IL |
| ZIP/Postal code |
61801 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA523814 |
| SRA |
SRP186600 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126939_RAW.tar |
11.9 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE126939_SHPKO_vs_WT.txt.gz |
505.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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