THE PATTERNS OF BINDING OF RAR, RXR AND TR HOMODIMERS AND HETERODIMERS TO DIRECT REPEATS ARE DICTATED BY THE BINDING SPECIFICITIES OF THE DNA-BINDING DOMAINS

被引:203
作者
MADER, S
CHEN, JY
CHEN, ZP
WHITE, J
CHAMBON, P
GRONEMEYER, H
机构
[1] FAC MED STRASBOURG,CNRS,GENET MOLEC EUCARYOTES LAB,11 RUE HUMANN,F-67085 STRASBOURG,FRANCE
[2] FAC MED STRASBOURG,INST CHIM BIOL,INSERM,U184,UNITE BIOL MOLEC & GENIE GENET 184,F-67085 STRASBOURG,FRANCE
关键词
DIMERIZATION; NUCLEAR RECEPTOR; RESPONSE ELEMENT; SPECIFIC DNA BINDING;
D O I
10.1002/j.1460-2075.1993.tb06196.x
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
We show here that, in addition to generating an increase in DNA binding efficiency, heterodimerization of retinoid X receptor (RXR) with either retinoic acid receptor (RAR) or thyroid hormone receptor (TR) alters the binding site repertoires of RAR, RXR and TR homodimers. The binding site specificities of both homo- and heterodimers appear to be largely determined by their DNA binding domains (DBDs), and are dictated by (i) homocooperative DNA binding of the RXR DBD, (ii) heterocooperative DNA binding of RXR/RAR and RXR/TR DBDs, and (iii) steric hindrance. No homodimerization domain exists in the DBDs of TR and RAR. The dimerization function which is located in the ligand binding domain further stabilizes, but in general does not change, the repertoire dictated by the corresponding DBD(s). The binding repertoire can be further modified by the actual sequence of the binding site. We also provide evidence supporting the view that the cooperative binding of the RXR/RAR and RXR/TR DBDs to directly repeated elements is anisotropic, with interactions between the dimerization interfaces occurring only with RXR bound to the 5' located motif. This polarity, which appears to be maintained in the full-length receptor heterodimers, may constitute a novel parameter in promoter-specific transactivation.
引用
收藏
页码:5029 / 5041
页数:13
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