Node

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]

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