ALL-TRANS AND 9-CIS RETINOIC ACID INDUCTION OF CRABPII TRANSCRIPTION IS MEDIATED BY RAR-RXR HETERODIMERS BOUND TO DR1 AND DR2 REPEATED MOTIFS
ALL-TRANS AND 9-CIS RETINOIC ACID INDUCTION OF CRABPII TRANSCRIPTION IS MEDIATED BY RAR-RXR HETERODIMERS BOUND TO DR1 AND DR2 REPEATED MOTIFS
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DOI：
10.1016/0092-8674(92)90267-g
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发表时间：
1992-10-02
期刊：
影响因子：
64.5
通讯作者：
CHAMBON, P
中科院分区：
文献类型：
--
作者：
DURAND, B;SAUNDERS, M;CHAMBON, P
细胞视黄酸结合蛋白II（CRABPII）基因中的两个协同视黄酸反应元件（RARE）介导P19胚胎癌细胞中视黄酸受体（RAR）和类维生素A X受体（RXR）的差异转录反式激活。RARE 1和RARE 2是分别由2bp（DR 2）和1bp（DR 1）分开的两个基序的直接重复（DR），并且比同二聚体更有效地结合RAR-RXR异二聚体。使用全反式和9-顺式RA，其差异激活RAR和RXR，以及RAR和RXR显性阴性突变体，结合RARE 1和RARE 2的RAR-RXR异二聚体被证明是负责CRABPII启动子反式激活，反对独特的DR间距指定RAR的识别。在异源二聚体中，RAR和RXR独立且差异地反式激活，这取决于特定的RARE。与这些结果一致，9-顺式RA比全反式RA更有效地增加CRABPII mRNA水平。相反，全反式和9-顺式RA对RAR β 2转录物的诱导具有相同的作用。
Two cooperating retinoic acid response elements (RAREs) in the cellular retinoic acid-binding protein II (CRABPII) gene mediate differential transcriptional transactivation by retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in P19 embryonal carcinoma cells. RARE1 and RARE2 are direct repeats (DR) of two motifs separated by 2 bp (DR2) and 1 bp (DR1), respectively, and bind RAR-RXR heterodimers more efficiently than homodimers. Using all-trans and 9-cis RA, which differentially activate RARs and RXRs, and RAR and RXR dominant-negative mutants, RAR-RXR heterodimers bound to RARE1 and RARE2 are shown to be responsible for CRABPII promoter transactivation, arguing against a unique DR spacing specifying recognition by RARs. Within heterodimers, RAR and RXR independently and differentially transactivate, depending on the specific RARE. Consistent with these results, 9-cis RA increases CRABPII mRNA levels more efficiently than all-trans RA. In contrast, all-trans and 9-cis RA have identical effects on induction of RARbeta2 transcripts.