help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on January 23, 2007
Molecular Endocrinology, doi:10.1210/me.2006-0208
Molecular Endocrinology Vol. 0, No. 2007 200602081-
doi:10.1210/me.2006-0208
Copyright © 2007 by the Endocrine Society.
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
21/4/865    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Matsushita, A.
Right arrow Articles by Nakamura, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matsushita, A.
Right arrow Articles by Nakamura, H.

Submitted on May 16, 2006
Accepted on January 16, 2007

Essential role of GATA2 in the negative regulation of thyrotropin {beta} gene by thyroid hormone and its receptors

Akio Matsushita, Shigekazu Sasaki*, Yumiko Kashiwabara, Koji Nagayama, Kenji Ohba, Hiroyuki Iwaki, Hiroko Misawa, Keiko Ishizuka, and Hirotoshi Nakamura

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Japan

* To whom correspondence should be addressed. E-mail: sasakis{at}hama-med.ac.jp.

Previously we reported that the negative regulation of the thyrotropin (TSH) {beta} gene by triiodothyronine (T3) and its receptor (TR) is observed in CV1 cells when GATA2 and Pit1 are introduced. Using this system, we further studied the mechanism of TSH{beta} inhibition. The negative regulatory element (NRE), which had been reported to mediate T3-bound TR (T3-TR) dependent inhibition, is dispensable, since deletion or mutation of NRE did not impair suppression. The reporter construct, TSH{beta}-D4-CAT, which possesses only the binding sites for Pit1 and GATA2, was activated by GATA2 alone, and this transactivation was specifically inhibited by T3-TR. The Zn-finger region of GATA2 interacts with the DNA binding domain (DBD) of TR T3-independently. The suppression by T3-TR was impaired by overexpression of a dominant negative type TR associated protein (TRAP) 220, an N- and C-terminal deletion construct, indicating the participation of TRAP220. Chromatin immunoprecipitation assays with a thyrotroph cell line, T{alpha}T1, revealed that T3 treatment recruited histone deacetylase 3, reduced the acetylation of histone H4, and caused the dissociation of TRAP220 within 15-30 min. The reduction of histone H4 acetylation was transient, while the dissociation of TRAP220 persisted for a longer period. In the negative regulation of the TSH{beta} gene by T3-TR we report that (1) GATA2 is the major transcriptional activator of the TSH{beta} gene, (2) the putative NRE previously reported is not required, (3) TR-DBD directly interacts with the Zn finger region of GATA2, and (4) histone deacetylation and TRAP220 dissociation are important.
Key words: TSH • thyroid hormone • thyroid hormone receptor • GATA2 • Pit1 • histone acetylation • TRAP220

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  TRβ  |  RARα  |  VDR
Coregulators:   TRAP220
Ligands:   Thyroid hormone



This article has been cited by other articles:


Home page
 J EndocrinolHome page
K. Nagayama, S. Sasaki, A. Matsushita, K. Ohba, H. Iwaki, H. Matsunaga, S. Suzuki, H. Misawa, K. Ishizuka, Y. Oki, et al.
Inhibition of GATA2-dependent transactivation of the TSH{beta} gene by ligand-bound estrogen receptor {alpha}
J. Endocrinol., October 1, 2008; 199(1): 113 - 125.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
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]

Home page
 Mol. Cell. Biol.Home page
H. Ohguchi, T. Tanaka, A. Uchida, K. Magoori, H. Kudo, I. Kim, K. Daigo, I. Sakakibara, M. Okamura, H. Harigae, et al.
Hepatocyte Nuclear Factor 4{alpha} Contributes to Thyroid Hormone Homeostasis by Cooperatively Regulating the Type 1 Iodothyronine Deiodinase Gene with GATA4 and Kruppel-Like Transcription Factor 9
Mol. Cell. Biol., June 15, 2008; 28(12): 3917 - 3931.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2007 by The Endocrine Society