Related Experiment Videos
Alien/CSN2 gene expression is regulated by thyroid hormone in rat brain.
Stephan P Tenbaum1, Stefan Juenemann, Thomas Schlitt
1Instituto de Investigaciones Biomédicas CSIC/UAM, C/ Arturo Duperier 4, 28029, Madrid, Spain.
Developmental Biology
|February 28, 2003
Summary
Alien, a corepressor for thyroid hormone receptor (TR), is regulated by thyroid hormone. Its gene expression and protein levels decrease in hypothyroid states, indicating a negative feedback loop in TR-mediated gene silencing.
Area of Science:
- Endocrinology
- Molecular Biology
- Gene Regulation
Background:
- Alien functions as a corepressor for the thyroid hormone receptor (TR).
- Corepressors are crucial for gene silencing mediated by DNA-bound transcriptional repressors.
Purpose of the Study:
- To investigate the regulation of Alien gene expression by thyroid hormone in vivo and in cell culture.
- To elucidate the role of TR in mediating thyroid hormone-induced Alien expression.
Main Methods:
- In situ hybridization to assess Alien mRNA distribution in mouse embryos and rat brains.
- Northern and Western blot analyses to detect Alien mRNAs and proteins.
- Hormonal induction studies in vivo and in cultured cells, including TR-deficient cells.
Main Results:
- Alien gene expression is widely distributed in the mouse embryo and rat brain.
- Hypothyroid animals show reduced Alien mRNA and protein levels.
- Thyroid hormone induces Alien expression both in vivo and in cell culture, mediated by TRalpha or TRbeta.
- Two distinct Alien mRNAs and proteins were detected, one being the CSN2 subunit of the COP9 signalosome.
- Both Alien forms are regulated by thyroid hormone.
Conclusions:
- Alien gene expression is directly controlled by thyroid hormone and TR.
- This regulation suggests a negative feedback mechanism between TR and its corepressor.
- Reduced corepressor levels may be a key control mechanism in TR-mediated gene silencing.