Retinoid X receptor alters the determination of DNA binding specificity by the P-box amino acids of the thyroid hormone receptor

被引:17
作者
Nelson, CC [1 ]
Hendy, SC [1 ]
Faris, JS [1 ]
Romaniuk, PJ [1 ]
机构
[1] UNIV VICTORIA,DEPT BIOCHEM & MICROBIOL,VICTORIA,BC V8W 3P6,CANADA
关键词
D O I
10.1074/jbc.271.32.19464
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear hormone receptors bind to hormone response elements in DNA consisting of two half-sites of 6 base pairs. The P-box amino acids of each receptor determine the identities of the central nucleotides of the half-site, 57 P-box variants of the human thyroid hormone receptor (hT3R beta) were used to demonstrate the relationship between P-box sequence and DNA binding specificity by homodimers and heterodimers formed with the retinoid X receptor (RXR). In general, the formation of heterodimers relieved many of the constraints on the compatibility of hT3R beta P-box sequences with DNA binding. Effects were most dramatic for heterodimers bound to a direct repeat spaced by four base pairs. RXR also overrides the P-box-derived DNA binding specificity of hT3R beta when heterodimers are bound to inverted or everted repeat elements, These effects of RXR are most pronounced on AGGTCA half-sites but are squelched when the RXR partner of the heterodimer is bound to an AGGACA half-site. The influence of RXR on hT3R beta DNA binding specificity varies with the orientation of half-sites in the element, the identity of the fourth base pair of the half-site, and the spacing between the half-sites of direct repeats. These differences suggest that the DNA binding domains of RXR-hT3R beta heterodimers are not positioned equivalently on the various elements, affecting the manner in which the P-box amino acids of hT3R beta interact with base pairs within the half-site.
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页码:19464 / 19474
页数:11
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