DNA binding and interaction with the nuclear receptor corepressor of thyroid hormone receptor are required for ligand-independent stimulation of the mouse preprothyrotropin-releasing hormone gene

被引:25
作者
Satoh, T
Monden, T
Ishizuka, T
Mitsuhashi, T
Yamada, M
Mori, M
机构
[1] Gunma Univ, Sch Med, Dept Internal Med 1, Maebashi, Gumma 3718511, Japan
[2] Univ Tokyo, Fac Med, Dept Internal Med 3, Tokyo 113, Japan
关键词
corepressor; mouse TRH gene; negative regulation; thyroid hormone receptor;
D O I
10.1016/S0303-7207(99)00032-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A negative thyroid hormone response element (TRE) in the mouse preprothyrotropin-releasing hormone (TRH) gene was previously mapped within the proximal promoter element between - 83 and + 53 that contained a TRE half-site motif at - 57 ((-57)TGACCT(-52)). In transfection experiments, the promoter activity is stimulated by unliganded thyroid hormone receptor (TR) and T-3 reverses the basal promoter stimulation. In this study, we determined whether the direct binding of TR to the TRE half-site in the mouse TRH gene is required for the ligand-independent stimulation using a transient transfection assay into CV-1 cells and electrophoretic mobility shift assays (EMSA). In addition, the role of a corepressor protein for the ligand-independent stimulation was examined using a putative splicing variant of the nuclear receptor corepressor (N-CoRI). Point mutations introduced into the TRE half-site at - 57 eliminated the binding of TR and the stimulatory effect of unliganded TR. Two mutant TRs lacking DNA-binding activity and two CoR box mutant TRs showed no stimulation in the wild-type TRH promoter. The cotransfected N-CoRI potentiated the ligand-independent stimulation by the wild-type TR, but did not compensate for the impaired function of the CoR box mutant TR. In EMSA, TR strongly bound as homodimers and weakly as heterodimers with retinoid X receptor (RXR) to the element containing the TRE half-site at - 57. Binding of TR to the TRE half-site was essential to form homo- and heterodimers, and the RXR binding site appeared to be located downstream of the TRE half-site. In vitro translated N-CoRI preferentially bound TR homodimers over TR/RXR heterodimers. These results collectively suggest that the DNA-bound TR/corepressor complex might be directly involved in the ligand-independent stimulation of the mouse TRH gene promoter. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:137 / 149
页数:13
相关论文
共 55 条
  • [41] Negative regulation of the gene for the preprothyrotropin-releasing hormone from the mouse by thyroid hormone requires additional factors in conjunction with thyroid hormone receptors
    Satoh, T
    Yamada, M
    Iwasaki, T
    Mori, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) : 27919 - 27926
  • [42] THYROID-HORMONE REGULATES TRH BIOSYNTHESIS IN THE PARAVENTRICULAR NUCLEUS OF THE RAT HYPOTHALAMUS
    SEGERSON, TP
    KAUER, J
    WOLFE, HC
    MOBTAKER, H
    WU, P
    JACKSON, IMD
    LECHAN, RM
    [J]. SCIENCE, 1987, 238 (4823) : 78 - 80
  • [43] Nuclear receptor corepressors activate rather than suppress basal transcription of genes that are negatively regulated by thyroid hormone
    Tagami, T
    Madison, LD
    Nagaya, T
    Jameson, JL
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (05) : 2642 - 2648
  • [44] Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator
    Takeshita, A
    Yen, PM
    Misiti, S
    Cardona, GR
    Liu, Y
    Chin, WW
    [J]. ENDOCRINOLOGY, 1996, 137 (08) : 3594 - 3597
  • [45] PROMOTER INDEPENDENT DOWN-REGULATION OF THE FIREFLY LUCIFERASE GENE BY T(3) AND T(3) RECEPTOR IN CV1 CELLS
    TILLMAN, JB
    CRONE, DE
    KIM, HS
    SPRUNG, CN
    SPINDLER, SR
    [J]. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1993, 95 (1-2) : 101 - 109
  • [46] Novel regulation of keratin gene expression by thyroid hormone and retinoid receptors
    TomicCanic, M
    Day, D
    Samuels, HH
    Freedberg, IM
    Blumenberg, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (03) : 1416 - 1423
  • [47] DIRECT REPEATS AS SELECTIVE RESPONSE ELEMENTS FOR THE THYROID-HORMONE, RETINOIC ACID, AND VITAMIN-D3 RECEPTORS
    UMESONO, K
    MURAKAMI, KK
    THOMPSON, CC
    EVANS, RM
    [J]. CELL, 1991, 65 (07) : 1255 - 1266
  • [48] THE C-ERB-A GENE ENCODES A THYROID-HORMONE RECEPTOR
    WEINBERGER, C
    THOMPSON, CC
    ONG, ES
    LEBO, R
    GRUOL, DJ
    EVANS, RM
    [J]. NATURE, 1986, 324 (6098) : 641 - 646
  • [49] The thyrotropin-releasing hormone gene 1998: Cloning, characterization, and transcriptional regulation in the central nervous system, heart, and testis
    Wilber, JF
    Xu, AH
    [J]. THYROID, 1998, 8 (10) : 897 - 901
  • [50] WILKSTROM L, 1998, EMBO J, V17, P455, DOI DOI 10.1093/EMBOJ/17.2.455