Abstract
Thyroid hormone (TH) plays a critical role in development, growth, and metabolism by binding to nuclear TH receptors to modulate gene expression. In the absence of TH, TH receptors repress genes that are TH-activated by recruiting the nuclear receptor corepressor (NCoR), which exists in a tight complex with histone deacetylase 3 (HDAC3). Here we explored the actions of TH in the deacetylase activating domain mutant (DADm) mouse, whose NCoR-HDAC3 interaction is genetically disrupted. Several TH-activated genes were derepressed in the liver of euthyroid and hypothyroid DADm mice, consistent with the corepressor paradigm and a critical role of the NCoR-HDAC3 interaction in basal repression. The role of corepressors in genes that are down-regulated by TH is less well understood. Remarkably, circulating TSH levels were increased in euthyroid DADm mice, and the pituitary expression of TSHα, a classic TH-down-regulated gene, was modestly but significantly elevated regardless of TH status. Thus, the NCoR interaction with HDAC3 modulates expression of both positively- and negatively-regulated genes by TH in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1359-1367 |
| Number of pages | 9 |
| Journal | Molecular Endocrinology |
| Volume | 24 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Endocrinology
- Medicine(all)
Cite this
The interaction between nuclear receptor corepressor and histone deacetylase 3 regulates both positive and negative thyroid hormone action in vivo. / You, Seo Hee; Liao, Xiaohui; Weiss, Roy E; Lazar, Mitchell A.
In: Molecular Endocrinology, Vol. 24, No. 7, 2010, p. 1359-1367.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The interaction between nuclear receptor corepressor and histone deacetylase 3 regulates both positive and negative thyroid hormone action in vivo
AU - You, Seo Hee
AU - Liao, Xiaohui
AU - Weiss, Roy E
AU - Lazar, Mitchell A.
PY - 2010
Y1 - 2010
N2 - Thyroid hormone (TH) plays a critical role in development, growth, and metabolism by binding to nuclear TH receptors to modulate gene expression. In the absence of TH, TH receptors repress genes that are TH-activated by recruiting the nuclear receptor corepressor (NCoR), which exists in a tight complex with histone deacetylase 3 (HDAC3). Here we explored the actions of TH in the deacetylase activating domain mutant (DADm) mouse, whose NCoR-HDAC3 interaction is genetically disrupted. Several TH-activated genes were derepressed in the liver of euthyroid and hypothyroid DADm mice, consistent with the corepressor paradigm and a critical role of the NCoR-HDAC3 interaction in basal repression. The role of corepressors in genes that are down-regulated by TH is less well understood. Remarkably, circulating TSH levels were increased in euthyroid DADm mice, and the pituitary expression of TSHα, a classic TH-down-regulated gene, was modestly but significantly elevated regardless of TH status. Thus, the NCoR interaction with HDAC3 modulates expression of both positively- and negatively-regulated genes by TH in vivo.
AB - Thyroid hormone (TH) plays a critical role in development, growth, and metabolism by binding to nuclear TH receptors to modulate gene expression. In the absence of TH, TH receptors repress genes that are TH-activated by recruiting the nuclear receptor corepressor (NCoR), which exists in a tight complex with histone deacetylase 3 (HDAC3). Here we explored the actions of TH in the deacetylase activating domain mutant (DADm) mouse, whose NCoR-HDAC3 interaction is genetically disrupted. Several TH-activated genes were derepressed in the liver of euthyroid and hypothyroid DADm mice, consistent with the corepressor paradigm and a critical role of the NCoR-HDAC3 interaction in basal repression. The role of corepressors in genes that are down-regulated by TH is less well understood. Remarkably, circulating TSH levels were increased in euthyroid DADm mice, and the pituitary expression of TSHα, a classic TH-down-regulated gene, was modestly but significantly elevated regardless of TH status. Thus, the NCoR interaction with HDAC3 modulates expression of both positively- and negatively-regulated genes by TH in vivo.
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U2 - 10.1210/me.2009-0501
DO - 10.1210/me.2009-0501
M3 - Article
C2 - 20427468
AN - SCOPUS:77954832705
VL - 24
SP - 1359
EP - 1367
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 7
ER -