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| Status |
Public on Aug 08, 2009 |
| Title |
Isoform-specific transcriptional activity of overlapping targets that respond to thyroid hormone receptors a1 and b1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that control multiple aspects of physiology and development. TRs are expressed in vertebrates as a series of distinct isoforms that exert distinct biological roles. We wished to determine if the two most widely expressed isoforms, TRa1 and TRb1, exert their different biological effects by regulating different sets of target genes. Using stably transformed HepG2 cells and a microarray analysis, we were able to demonstrate that TRa1 and TRb1 regulate a largely overlapping repertoire of target genes in response to T3 hormone. However, these two isoforms display very different transcriptional properties on each individual target gene, ranging from a much greater T3-mediated regulation by TRa1 than by TRb1, to near equal regulation by both isoforms. We also identified TRa1 and TRb1 target genes that were regulated by these receptors in a hormone-independent fashion. We suggest that it is this gene-specific, isoform-specific amplitude of transcriptional regulation that is the likely basis for the appearance and maintenance of TRa1 and TRb1 over evolutionary time. In essence, TRa1 and TRb1 adjust the magnitude of the transcriptional response at different target genes to different levels; by altering the ratio of these isoforms in different tissues or at different developmental times, the intensity of T3 response can be individually tailored to different physiological and developmental requirements.
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| Overall design |
TRa1, TRb1, or empty plasmid control stably transfected HepG2 cells were treated with 100 nM T3 or with ethanol carrier alone for 6h. Three independent biological repeats were analyzed for each of the three transformant pools (empty plasmid control, TRa1, and TRb1).
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| Contributor(s) |
Chan IH, Privalsky ML |
| Citation(s) |
19628582 |
| Submission date |
Aug 07, 2009 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Michael L Goodson |
| E-mail(s) |
mlgoodson@ucdavis.edu
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| Organization name |
University of California Davis
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| Department |
SVM:APC
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| Street address |
One Shields Ave
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA118663 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17561_RAW.tar |
118.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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