DNA recognition by thyroid hormone and retinoic acid receptors: 3,4,5 rule modified.
DNA recognition by thyroid hormone and retinoic acid receptors: 3,4,5 rule modified.
复制标题
DOI：
10.1016/j.mce.2009.11.010
复制
发表时间：
2010-05-05
影响因子：
4.1
通讯作者：
Privalsky ML
中科院分区：
文献类型：
--
作者：
Phan TQ;Jow MM;Privalsky ML
已有研究认为，维甲酸受体(RARs)和甲状腺激素受体(TRs)都与AGGTCA的“半位点”序列结合，但通过识别不同的半位点间距来区分它们不同的靶基因。我们在这里报道，基于这些AGGTCA半位点的人工DNA结合位点具有高亲和力，但特异性较差，仅靠间距并不能解释TRS和RAR的不同DNA识别特性。相反，我们已经确定，存在于自然产生的RAR和TR靶基因中的非共识半位点在定义受体DNA识别特异性方面起着至关重要的作用，并与侧翼序列和半位点间距一起在体外产生受体特异性DNA结合。我们还提供了证据，证明细胞中的辅助蛋白产生额外的受体特异性靶基因识别，部分是通过破坏核受体与“错误”反应元件的结合而实现的。
It has been proposed that retinoic acid receptors (RARs) and thyroid hormone receptors (TRs) both bind to AGGTCA “half-site” sequences, but distinguish their different target genes by recognizing different half-site spacings. We report here that artificial DNA binding sites based on these AGGTCA half-sites confer high affinity, but poor specificity, and that spacing alone does not account for the divergent DNA recognition properties of TRs and RARs. Instead, we have determined that the non-consensus half-sites that are present in naturally occurring RAR and TR target genes play a crucial role in defining receptor DNA recognition specificity, and work together with flanking sequences and half-site spacing to produce receptor-specific DNA binding in vitro. We also provide evidence that auxiliary proteins in cells generate an additional layer of receptor-specific target gene recognition, in part by destabilizing the binding of nuclear receptors to the “wrong” response elements.
登录
查看更多内容
影响因子：
2.9
作者：
GUAN, KL;DIXON, JE
通讯作者：
DIXON, JE
影响因子：
--
作者：
FORMAN, BM;CASANOVA, J;SAMUELS, HH
通讯作者：
SAMUELS, HH
影响因子：
5.3
作者：
CHEN, HW;PRIVALSKY, ML
通讯作者：
PRIVALSKY, ML
影响因子：
--
作者：
ADAN, RAH;COX, JJ;BURBACH, JPH
通讯作者：
BURBACH, JPH
影响因子：
4.8
作者：
Judelson, C;Privalsky, ML
通讯作者：
Privalsky, ML