Three steps in the regulation of transcription by the thyroid hormone receptor: establishment of a repressive chromatin structure, disruption of chromatin and transcriptional activation

1997 ◽  
Vol 25 (2) ◽  
pp. 612-615 ◽  
Author(s):  
A. P. Wolffe ◽  
J. Wong ◽  
Q. Li ◽  
B.-Z. Levi ◽  
Y.-B. Shi
Keyword(s):  
Thyroid Hormone ◽  
Chromatin Structure ◽  
Transcriptional Activation ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Regulation Of Transcription ◽  
Repressive Chromatin

scholarly journals Mutations in the conserved C-terminal sequence in thyroid hormone receptor dissociate hormone-dependent activation from interference with AP-1 activity.

1997 ◽  
Vol 17 (8) ◽  
pp. 4687-4695 ◽  
Author(s):  
F Saatcioglu ◽  
G Lopez ◽  
B L West ◽  
E Zandi ◽  
W Feng ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Mutational Analysis ◽  
Binding Domain ◽  
Yeast Cells ◽  
Terminal Sequence

A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and conserved in members of the nuclear receptor superfamily is required for normal biological function of its normal cellular counterpart, the thyroid hormone receptor alpha (T3R alpha). We carried out an extensive mutational analysis of this region based on the crystal structure of the hormone-bound ligand binding domain of T3R alpha. Mutagenesis of Leu398 or Glu401, which are surface exposed according to the crystal structure, completely blocks or significantly impairs T3-dependent transcriptional activation but does not affect or only partially diminishes interference with AP-1 activity. These are the first mutations that clearly dissociate these activities for T3R alpha. Substitution of Leu400, which is also surface exposed, does not affect interference with AP-1 activity and only partially diminishes T3-dependent transactivation. None of the mutations affect ligand-independent transactivation, consistent with previous findings that this activity is mediated by the N-terminal domain of T3R alpha. The loss of ligand-dependent transactivation for some mutants can largely be reversed in the presence of GRIP1, which acts as a strong ligand-dependent coactivator for wild-type T3R alpha. There is excellent correlation between T3-dependent in vitro association of GRIP1 with T3R alpha mutants and their ability to support T3-dependent transcriptional activation. Therefore, GRIP1, previously found to interact with the glucocorticoid, estrogen, and androgen receptors, may also have a role in T3R alpha-mediated ligand-dependent transcriptional activation. When fused to a heterologous DNA binding domain, that of the yeast transactivator GAL4, the conserved C terminus of T3R alpha functions as a strong ligand-independent activator in both mammalian and yeast cells. However, point mutations within this region have drastically different effects on these activities compared to their effect on the full-length T3R alpha. We conclude that the C-terminal conserved region contains a recognition surface for GRIP1 or a similar coactivator that facilitates its interaction with the basal transcriptional apparatus. While important for ligand-dependent transactivation, this interaction surface is not directly involved in transrepression of AP-1 activity.

Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4

2013 ◽  
Vol 439 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Hsiang-Cheng Chi ◽  
Chen-Hsin Liao ◽  
Ya-Hui Huang ◽  
Sheng-Ming Wu ◽  
Chung-Ying Tsai ◽  
...  
Keyword(s):  
Cell Migration ◽  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hepatoma Cell

scholarly journals Involvement of Histone Methylation and Phosphorylation in Regulation of Transcription by Thyroid Hormone Receptor

2002 ◽  
Vol 22 (16) ◽  
pp. 5688-5697 ◽  
Author(s):  
Jiwen Li ◽  
Qiushi Lin ◽  
Ho-Geun Yoon ◽  
Zhi-Qing Huang ◽  
Brian D. Strahl ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Histone Acetylation ◽  
Histone Methylation ◽  
Hormone Receptor ◽  
Transcriptional Control ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Nuclear Hormone Receptors ◽  
Regulation Of Transcription

ABSTRACT Previous studies have established an important role of histone acetylation in transcriptional control by nuclear hormone receptors. With chromatin immunoprecipitation assays, we have now investigated whether histone methylation and phosphorylation are also involved in transcriptional regulation by thyroid hormone receptor (TR). We found that repression by unliganded TR is associated with a substantial increase in methylation of H3 lysine 9 (H3-K9) and a decrease in methylation of H3 lysine 4 (H3-K4), methylation of H3 arginine 17 (H3-R17), and a dual modification of phosphorylation of H3 serine 10 and acetylation of lysine 14 (pS10/acK14). On the other hand, transcriptional activation by liganded TR is coupled with a substantial decrease in both H3-K4 and H3-K9 methylation and a robust increase in H3-R17 methylation and the dual modification of pS10/acK14. Trichostatin A treatment results in not only histone hyperacetylation but also an increase in methylation of H3-K4, increase in dual modification of pS10/acK14, and reduction in methylation of H3-K9, revealing an extensive interplay between histone acetylation, methylation, and phosphorylation. In an effort to understand the underlying mechanism for an increase in H3-K9 methylation during repression by unliganded TR, we demonstrated that TR interacts in vitro with an H3-K9-specific histone methyltransferase (HMT), SUV39H1. Functional analysis indicates that SUV39H1 can facilitate repression by unliganded TR and in so doing requires its HMT activity. Together, our data uncover a novel role of H3-K9 methylation in repression by unliganded TR and provide strong evidence for the involvement of multiple distinct histone covalent modifications (acetylation, methylation, and phosphorylation) in transcriptional control by nuclear hormone receptors.

Role of the conserved C-terminal region of thyroid hormone receptor-α in ligand-dependent transcriptional activation

1998 ◽  
Vol 138 (1-2) ◽  
pp. 105-114 ◽  
Author(s):  
Samia Selmi-Ruby ◽  
Juan Casanova ◽  
Sunil Malhotra ◽  
Bernard Roussett ◽  
Bruce M Raaka ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Terminal Region ◽  
Thyroid Hormone Receptor Α
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