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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0099v1 42/3/225    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kashiwabara, Y. Articles by Nakamura, H. Search for Related Content PubMed PubMed Citation Articles by Kashiwabara, Y. Articles by Nakamura, H.

Y Kashiwabara, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan
S Sasaki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan
A Matsushita, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
K Nagayama, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
K Ohba, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Iwaki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Matsunaga, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
S Suzuki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Misawa, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
K Ishizuka, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
Y Oki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Nakamura, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence: Shigekazu Sasaki, Email: sasakis{at}hama-med.ac.jp

Abstract

Thyrotropin (thyroid stimulating hormone, TSH) is a heterodimer consisting of and β chains, and the β chain (TSHβ) is specific to TSH. The coexistence of two transcription factors, Pit1 and GATA2, is known to be essential for TSHβ expression. Using kidney-derived CV1 cells, we investigated the role of Pit1 in the expression of TSHβ gene. GATA2 Zn finger domain, which is known to recognize GATA-responsive elements (GATA-REs), is essential for cooperation by Pit1. Transactivation of TSHβ promoter requires Pit1-binding site upstream to GATA-REs (Pit1-US) and the spacing between Pit1-US and GATA-REs strictly determines the cooperation between Pit1 and GATA2. Moreover, truncation of the sequence downstream to GATA-REs enabled GATA2 to transactivate the TSHβ promoter without Pit1. The deleted region (nt –82/–52) designated as a suppressor region (SR) was considered to inhibit transactivation by GATA2. The cooperation of Pit1 with GATA2 was not conventional synergism but rather counteracted SR-induced suppression (derepression). The minimal sequence for SR was mapped to the 9 bp sequence downstream to GATA-REs. Electrophoretic mobility shift assay suggested that some nuclear factor exists in CV1 cells which binds with SR and this interaction was blocked by recombinant Pit1. Our study indicates that major activator for the TSHβ promoter is GATA2 and that Pit1 protects the function of GATA2 from the inhibition by SR-binding protein.