NCBI Gene
| Symbol | tle3 | Gene ID | 7090 |
| IF | 3.6% | Link Number | 4 |
| Full Name | transducin-like enhancer of split 3 | ||
| Aliases | ESG,ESG3,GRG3,HsT18976 | ||
| Summary | This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013] |
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Node Summary
PMID: 21459326
Groucho family member transducin-like enhancer 3 (TLE3) is a PPARγ co-activator that must be induced during adipogenesis and is recruited to PPARγ target genes during terminal differentiation.
PMID: 21459326
TLE3 antagonizes TCF4 activation by β-catenin in preadipocytes, thereby inhibiting Wnt target gene expression and reversing β-catenin-dependent repression of adipocyte gene expression.
PMID: 23880346
We found that TLE3 strongly suppressed ALP activity and OSE2-luciferase activity induced by Runx2 and this repression of Runx2 by TLE3 occurs via HDACs because treatment with TSA, a class I and II HDAC inhibitor, rescued this repression. In conclusion, we identify TLE3 as a suppressor of BMSC differentiation in osteoblast lineage cells in vitro. Our data suggest that TLE3 activity may be a key in balancing adipocyte and osteoblast differentiation in the adult bone marrow microenvironment.
PMID: 24444608
Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family members, targets Runx2 transcription and suppresses osteoblast differentiation in bone marrow stromal cells (BMSCs).Here, we identify Wnt responsive elements of the TLE3 promoter region through comparative genomic and functional analyses and show that expression of TLE3 is increased by Wnt signaling, which is important for osteoblast differentiation. We also demonstrated that TLE3 is able to suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation.
PMID: 21459326
TLE3 is a direct target of PPARγ that participates in a feed-forward loop during adipocyte differentiation. TLE3 enhances PPARγ activity and functions synergistically with PPARγ on its target promoters to stimulate adipogenesis. At the same time, induction of TLE3 during differentiation provides a mechanism for termination of Wnt signaling. TLE3 antagonizes TCF4 activation by β-catenin in preadipocytes, thereby inhibiting Wnt target gene expression and reversing β-catenin-dependent repression of adipocyte gene expression.
Node Expression
| # | PMID | Condition | Expression | Material | |
|---|---|---|---|---|---|
| 1 | 23894377 | control VS cold-induced Liver (1 2) | (1 2.0642903) | mouse |
Relation Chart
Chart Legend
Relation Table (4 records)
| # | Source | IF(%) | Relation | Target | IF(%) | Type | Method | PMID |
|---|---|---|---|---|---|---|---|---|
| 1 | pparg | 77.1 | activates | tle3 | 3.6 | bind to DNA | ChIP,Reporter,Overexpression and knockdown | 21459326 |
| 2 | tle3 | 3.6 | activates | pparg | 77.1 | bind to protein | Cell culture and differentiation,ChIP,Immunofluorescence,Reporter,Overexpression and knockdown | 21459326 |
| 3 | tle3 | 3.6 | inhibits | tcf4 | 10.8 | others | Cell culture and differentiation,ChIP,Reporter,Overexpression and knockdown | 21459326 |
| 4 | wnt | 3.5 | activates | tle3 | 3.6 | bind to DNA | Bioinformatic,Reporter | 24444608 |
Prediction Chart
Chart Legend
Prediction Table (19 records)
| # | Source | IF(%) | Target | IF(%) | Species | Agreement | Computational Predictions / PMID |
|---|---|---|---|---|---|---|---|
| 1 | mirn10a | 7.3 | tle3 | 3.6 | Human | 212.00 | 2 |
| 2 | mirn10a | 7.3 | tle3 | 3.6 | Human | 100.00 | 2 |
| 3 | mirn222 | 12.6 | tle3 | 3.6 | Human | 100.00 | 1 |
| 4 | mirn222 | 12.6 | tle3 | 3.6 | Human | 252.00 | 1 |
| 5 | mirn2861 | 12.3 | tle3 | 3.6 | Mouse | -0.04 | 3 |
| 6 | mirn34a | 19.1 | tle3 | 3.6 | Human | 262.00 | 1 |
| 7 | mirn34a | 19.1 | tle3 | 3.6 | Human | 100.00 | 1 |
| 8 | tle3 | 3.6 | fabp4 | 33.1 | Human | 100.00 | 21459326 |
| 9 | tle3 | 3.6 | cd36 | 11.6 | Human | 100.00 | 21459326 |
| 10 | tle3 | 3.6 | ephx2 | 4.2 | Human | 100.00 | 21459326 |
| 11 | tle3 | 3.6 | adipoq | 27.1 | Human | 100.00 | 21459326 |
| 12 | tle3 | 3.6 | ucp2 | 11.7 | Human | 100.00 | 21459326 |
| 13 | tle3 | 3.6 | pex11a | 2.7 | Human | 100.00 | 21459326 |
| 14 | tle3 | 3.6 | atf3 | 13 | Human | 100.00 | 21459326 |
| 15 | tle3 | 3.6 | eno3 | 3.1 | Human | 100.00 | 21459326 |
| 16 | tle3 | 3.6 | mx1 | 1.7 | Human | 100.00 | 21459326 |
| 17 | tle3 | 3.6 | cxcl10 | 2.9 | Human | 100.00 | 21459326 |
| 18 | tle3 | 3.6 | peg10 | 4.8 | Human | 100.00 | 21459326 |
| 19 | tle3 | 3.6 | pnpla2 | 9.1 | Human | 100.00 | 21459326 |

