|
Originally published In Press as doi:10.1074/jbc.M207264200 on November 4, 2002
J. Biol. Chem., Vol. 278, Issue 2, 732-738, January 10, 2003
Thyroid Hormone Receptor DNA Binding Is Required for Both
Positive and Negative Gene Regulation*
Nobuyuki
Shibusawa ,
Anthony N.
Hollenberg§, and
Fredric E.
Wondisford ¶
From the Section of Endocrinology, Department of
Medicine, the University of Chicago, Chicago, Illinois 60637 and
§ Division of Endocrinology, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, Massachusetts 02215
The isoform of thyroid hormone receptor
(TR- ) has a key role in the feedback regulation of the
hypothalamic-pituitary-thyroid (H-P-T) axis. The mechanism of
trans-repression of the hypothalamic thyrotropin-releasing hormone
(TRH) and pituitary thyroid-stimulating hormone (TSH) subunit genes,
however, remains poorly understood. A number of distinct mechanisms for
TR- -mediated negative regulation by thyroid hormone have been
proposed, including those that require and do not require DNA binding.
To clarify the importance of DNA binding in negative regulation, we
constructed a DNA-binding mutant of TR- in which two amino acids
within the P box were altered (GSG for EGG) to
resemble that found in the glucocorticoid receptor (GR). We termed this
mutant GS125, and as expected, it displayed low binding affinities for
positive and negative thyroid hormone-response element (pTRE and nTRE,
respectively) in gel-mobility shift assays. In transient transfection
assays, the GS125 mutant abolished transactivation on three classic
pTREs (DR+4, LAP, and PAL) and all negatively regulated promoters in
the H-P-T axis (TRH, TSH- , and TSH- ). However, GS125 TR- bound
to a composite TR/GR-response element and was fully functional on this
hybrid TR/GR-response element. Moreover, the GS125 TR- mutant
displayed normal interactions with transcriptional cofactors in
mammalian two-hybrid assays. These data do not support a DNA-binding
independent mechanism for thyroid hormone negative regulation in the
H-P-T axis.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed: Section of
Endocrinology, Dept. of Medicine, the University of Chicago, 5841 S. Maryland Ave., MC 1027, Chicago, IL 60637. Tel.: 773-702-6217; Fax: 773-834-0486.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
D. S. Machado, A. Sabet, L. A. Santiago, A. R. Sidhaye, M. I. Chiamolera, T. M. Ortiga-Carvalho, and F. E. Wondisford
From the Cover: A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo
PNAS,
June 9, 2009;
106(23):
9441 - 9446.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. I. Chiamolera and F. E. Wondisford
Thyrotropin-Releasing Hormone and the Thyroid Hormone Feedback Mechanism
Endocrinology,
March 1, 2009;
150(3):
1091 - 1096.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Wulf, M. G Wetzel, M. Kebenko, M. Kroger, A. Harneit, J. Merz, and J. M Weitzel
The role of thyroid hormone receptor DNA binding in negative thyroid hormone-mediated gene transcription
J. Mol. Endocrinol.,
July 1, 2008;
41(1):
25 - 34.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Dong, C. L. Yauk, A. Williams, A. Lee, G. R. Douglas, and M. G. Wade
Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element
Endocrinology,
August 1, 2007;
148(8):
3932 - 3940.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld
Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks
Physiol Rev,
July 1, 2007;
87(3):
933 - 963.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. F. R. Velasco, M. Togashi, P. G. Walfish, R. P. Pessanha, F. N. Moura, G. B. Barra, P. Nguyen, R. Rebong, C. Yuan, L. A. Simeoni, et al.
Thyroid Hormone Response Element Organization Dictates the Composition of Active Receptor
J. Biol. Chem.,
April 27, 2007;
282(17):
12458 - 12466.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Matsushita, S. Sasaki, Y. Kashiwabara, K. Nagayama, K. Ohba, H. Iwaki, H. Misawa, K. Ishizuka, and H. Nakamura
Essential Role of GATA2 in the Negative Regulation of Thyrotropin {beta} Gene by Thyroid Hormone and Its Receptors
Mol. Endocrinol.,
April 1, 2007;
21(4):
865 - 884.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Flamant, K. Gauthier, and J. Samarut
Thyroid Hormones Signaling Is Getting More Complex: STORMs Are Coming
Mol. Endocrinol.,
February 1, 2007;
21(2):
321 - 333.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Calamita, M. Moreno, D. Ferri, E. Silvestri, P. Roberti, L. Schiavo, P. Gena, M. Svelto, and F. Goglia
Triiodothyronine modulates the expression of aquaporin-8 in rat liver mitochondria
J. Endocrinol.,
January 1, 2007;
192(1):
111 - 120.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Flamant, J. D. Baxter, D. Forrest, S. Refetoff, H. Samuels, T. S. Scanlan, B. Vennstrom, and J. Samarut
International Union of Pharmacology. LIX. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Thyroid Hormone Receptors
Pharmacol. Rev.,
December 1, 2006;
58(4):
705 - 711.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Hashimoto, M. Yamada, S. Matsumoto, T. Monden, T. Satoh, and M. Mori
Mouse Sterol Response Element Binding Protein-1c Gene Expression Is Negatively Regulated by Thyroid Hormone
Endocrinology,
September 1, 2006;
147(9):
4292 - 4302.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. M. Santos, V. Afonso, G. B. Barra, M. Togashi, P. Webb, F. A. R. Neves, N. Lomri, and A. Lomri
Negative Regulation of Superoxide Dismutase-1 Promoter by Thyroid Hormone
Mol. Pharmacol.,
September 1, 2006;
70(3):
793 - 800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Nygard, N. Becker, B. Demeneix, K. Pettersson, and M. Bondesson
Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.
J. Mol. Endocrinol.,
June 1, 2006;
36(3):
517 - 530.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. M. Storey, S. Gentile, H. Ullah, A. Russo, M. Muessel, C. Erxleben, and D. L. Armstrong
Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone
PNAS,
March 28, 2006;
103(13):
5197 - 5201.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Meng, P. Webb, Y.-F. Yang, M. Shuen, A. F. Yousef, J. D. Baxter, J. S. Mymryk, and P. G. Walfish
E1A and a nuclear receptor corepressor splice variant (N-CoRI) are thyroid hormone receptor coactivators that bind in the corepressor mode
PNAS,
May 3, 2005;
102(18):
6267 - 6272.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Temple, R. N. Cohen, S. R. Wondisford, C. Yu, D. Deplewski, and F. E. Wondisford
An Intact DNA-binding Domain Is Not Required for Peroxisome Proliferator-activated Receptor {gamma} (PPAR{gamma}) Binding and Activation on Some PPAR Response Elements
J. Biol. Chem.,
February 4, 2005;
280(5):
3529 - 3540.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Shen, Q.-L. Li, G. A. Brent, and T. C. Friedman
Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter
Am J Physiol Endocrinol Metab,
January 1, 2005;
288(1):
E236 - E245.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S.-W. Kim, S.-J. Hong, K. M. Kim, S.-C. Ho, E. C. So, J. W. Harney, and P. R. Larsen
A Novel Cell Type-Specific Mechanism for Thyroid Hormone-Dependent Negative Regulation of the Human Type 1 Deiodinase Gene
Mol. Endocrinol.,
December 1, 2004;
18(12):
2924 - 2936.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Ishii, M. Yamada, T. Satoh, T. Monden, K. Hashimoto, N. Shibusawa, K. Onigata, A. Morikawa, and M. Mori
Aberrant Dynamics of Histone Deacetylation at the Thyrotropin-Releasing Hormone Gene in Resistance to Thyroid Hormone
Mol. Endocrinol.,
July 1, 2004;
18(7):
1708 - 1720.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Guo, K. Bakal, Y. Minokoshi, and A. N. Hollenberg
Leptin Signaling Targets the Thyrotropin-Releasing Hormone Gene Promoter in Vivo
Endocrinology,
May 1, 2004;
145(5):
2221 - 2227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Villa, J. Santiago, B. Belandia, and A. Pascual
A Response Unit in the First Exon of the {beta}-Amyloid Precursor Protein Gene Containing Thyroid Hormone Receptor and Sp1 Binding Sites Mediates Negative Regulation by 3,5,3'-Triiodothyronine
Mol. Endocrinol.,
April 1, 2004;
18(4):
863 - 873.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Ishizuka and M. A. Lazar
The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor
Mol. Cell. Biol.,
August 1, 2003;
23(15):
5122 - 5131.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|