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E-GEOD-54192 - NCoR1 and SMRT play unique roles in thyroid hormone signaling in the liver

Status
Released on 21 November 2014, last updated on 30 November 2014
Organism
Mus musculus
Samples (9)
Array (1)
Protocols (7)
Description
NCoR1 (Nuclear receptor Co-Repressor) and SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptor) are well-recognized coregulators of nuclear receptor (NR) action. However, their unique roles in the regulation of thyroid hormone (TH) signaling in specific cell types have not been determined. To accomplish this we generated a mouse model that lacked function of either NCoR1 or SMRT or both in the liver only. Despite both corepressors being present in the liver, SMRT had no ability to regulate TH signaling when deleted in either euthyroid or hypothyroid animals. In contrast, disruption of NCoR1 action confirmed that it is the principal mediator of TH sensitivity in vivo. While SMRT played little role in TH signaling alone, when disrupted in combination with NCoR1 it greatly accentuated the activation of hepatic lipogenesis regulated by NCoR1. Thus, corepressor specificity exists in vivo and NCoR1 is the principal regulator of TH action in the liver. However, both NCoR1 and SMRT collaborate to control hepatic lipogenesis and lipid storage, which likely reflects their cooperative activity in regulating the action of multiple NRs including the thyroid hormone receptor (TR). RNA was extracted from livers from 3 individual mice for each group (Double-floxed, Liver specific-SMRT knock out, and Liver specific-double knock out); all were euthyroid, female mice
Experiment type
transcription profiling by array 
Contacts
Markus Jeitler <markus.jeitler@meduniwien.ac.at>, Hiroaki Shimizu, Tony Hollenberg
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-54192.idf.txt
Sample and data relationshipE-GEOD-54192.sdrf.txt
Raw data (1)E-GEOD-54192.raw.1.zip
Processed data (1)E-GEOD-54192.processed.1.zip
Array designA-GEOD-16570.adf.txt
Links