Yen P M, Wilcox E C, Hayashi Y, Refetoff S, Chin W W
Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Endocrinology. 1995 Jul;136(7):2845-51. doi: 10.1210/endo.136.7.7789309.
Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate target gene transcription. Interestingly, in the absence of ligand, TRs also can repress basal transcription of positively regulated target genes, suggesting that unliganded TR may have a distinct role in gene regulation. In this paper, DNA binding, truncation, and natural human TR beta mutants were used in cotransfection and electrophoretic mobility shift assays to study various aspects of TR-mediated basal repression. Presently, little is known about the role(s) of natural human TR beta mutants on basal repression. These results show that: 1) TR binding to DNA likely is required for basal repression; 2) the amino-terminal region of TR is not required for basal repression; 3) TR homodimer binding is not absolutely required for basal repression, as TR mutants that selectively form TR-retinoid X receptor heterodimers can mediate basal repression; and 4) TR mutants with poor T3-binding affinity likely have constitutive basal repression, even in the presence of ligand. These findings provide new insight on the mechanism of basal repression by unliganded TRs.
甲状腺激素受体（TRs）是依赖配体的转录因子，可调节靶基因转录。有趣的是，在没有配体的情况下，TRs也能抑制正调控靶基因的基础转录，这表明未结合配体的TR在基因调控中可能具有独特作用。在本文中，DNA结合、截短和天然人类TRβ突变体被用于共转染和电泳迁移率变动分析，以研究TR介导的基础抑制的各个方面。目前，对于天然人类TRβ突变体在基础抑制中的作用知之甚少。这些结果表明：1）TR与DNA的结合可能是基础抑制所必需的；2）TR的氨基末端区域对于基础抑制不是必需的；3）基础抑制并非绝对需要TR同二聚体结合，因为选择性形成TR-视黄酸X受体异二聚体的TR突变体可以介导基础抑制；4）T3结合亲和力差的TR突变体可能具有组成型基础抑制，即使在存在配体的情况下也是如此。这些发现为未结合配体的TRs的基础抑制机制提供了新的见解。
