Msx1 homeodomain transcription factor and TATA-binding protein interact to repress the expression of the glycoprotein hormone α subunit gene.
Studying the regulatory mechanism of the glycoprotein hormone α subunit (αGSU) gene in thyrotropes is essential for understanding the synthesis of functional thyroid-stimulating hormone (TSH). Here, we investigated the influence of a homeodomain transcription factor Msx1 (Msh homeobox 1) on αGSU expression in thyrotropes. The transient expression of Msx1 inhibited the activity of an αGSU reporter gene, as well as its endogenous mRNA level in thyrotrope-derived αTSH cells. Luciferase reporter assays with serial deletion constructs and a close examination of the sequences revealed that the putative Msx1 binding site (PMS) in the αGSU promoter is not responsible for Msx1-mediated transcriptional repression. We also identified the TATA-box binding protein (TBP) as an interacting protein in thyrotropes. Interaction of TBP with Msx1 attenuates the inhibitory effect of Msx1 on αGSU gene expression in a DNA binding-independent manner. Furthermore, transient transfection studies with mutant Msx1 revealed that the interaction of TBP and Msx1 is critical for Msx1-mediated transcriptional repression of the αGSU. These results suggest that Msx1 functions as a transcriptional repressor of αGSU and that its interaction with TBP is an integral part of the mechanism by which Msx1 regulates the inhibition of αGSU gene expression.
Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Republic of Korea.
Ki-Sun
KS
Park
Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Republic of Korea. Electronic address: kimkk@cnu.ac.kr.
Kee K
KK
Kim
Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Republic of Korea. Electronic address: kyoonkim@cnu.ac.kr.
Kyoon Eon
KE
Kim
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D006801:Humans; D051957:MSX1 Transcription Factor / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D060066:Protein Interaction Maps; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014158:Transcription, Genetic
D015292:Glycoprotein Hormones, alpha Subunit; D051957:MSX1 Transcription Factor; D035181:TATA-Box Binding Protein
Msx1; TBP; TSH; Transcriptional repression; αGSU