|
| Status |
Public on Dec 04, 2008 |
| Title |
Gene expression profiling in NCoR deficient mouse livers |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoR∆ID) that cannot interact with the TR. L-NCoR∆ID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoR∆ID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoR∆ID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3.
Keywords: NCoR, thyroid hormone signaling, mouse liver, DNA Microarray
|
| |
|
| Overall design |
To better assess the role of NCoR in positive and negative regulation we performed micorarray analysis of gene expression in the livers of euthyroid and hypothyroid control and L-NCoR∆ID mice.
|
| |
|
| Contributor(s) |
Astapova I, Bilban M, Hollenberg TH |
| Citation(s) |
19052228 |
| Submission date |
Dec 21, 2007 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Martin Bilban |
| E-mail(s) |
Martin.Bilban@meduniwien.ac.at
|
| Phone |
++43 (0)1 40400 6441
|
| Organization name |
Medical University of Vienna
|
| Department |
|
| Street address |
|
| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA108181 |
Less...
More...