Retinoic acid receptor α mediates all-trans-retinoic acid-induced Klf4 gene expression by regulating Klf4 promoter activity in vascular smooth muscle cells
| Autor: | Si Chen, Jin-kun Wen, Guo-yan Ma, Jian-hong Shi, Bin Zheng |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Transcriptional Activation Receptors Retinoic Acid Sp1 Transcription Factor Retinoic acid Kruppel-Like Transcription Factors Tretinoin CHO Cells Biology Response Elements Biochemistry Muscle Smooth Vascular chemistry.chemical_compound Kruppel-Like Factor 4 Cricetulus stomatognathic system Cricetinae Transcriptional regulation medicine Animals Promoter Regions Genetic Molecular Biology Transcription factor neoplasms Sp1 transcription factor organic chemicals Retinoic Acid Receptor alpha fungi Promoter Cell Biology Molecular biology biological factors Rats Retinoic acid receptor chemistry Retinoic acid receptor alpha Gene Knockdown Techniques embryonic structures cardiovascular system sense organs Y-Box-Binding Protein 1 biological phenomena cell phenomena and immunity medicine.drug Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 287(14) |
| ISSN: | 1083-351X |
| Popis: | The transcription factor Kruppel-like factor 4 (KLF4) plays a critical role in vascular smooth muscle cell (VSMC) differentiation induced by all-trans-retinoic acid (ATRA). Although it has been demonstrated that ATRA stimulation augments both KLF4 protein and mRNA levels in VSMCs, the molecular mechanisms by which ATRA regulates Klf4 transcription are unknown. In this study, we examined the roles of ATRA-selective nuclear retinoic acid receptors (RARs) in the transcriptional regulation of Klf4. The introduction of small interfering RNA and an RAR antagonist demonstrated that RARα, but not RARβ or RARγ, mediated ATRA-induced Klf4 expression. A luciferase assay for the Klf4 promoter showed that three GC boxes in the proximal Klf4 promoter were indispensible for ATRA-induced Klf4 transcription and that RARα enhanced Klf4 promoter activity in a GC box-dependent manner. Furthermore, chromatin immunoprecipitation and oligonucleotide pulldown assays demonstrated that the transcription factors KLF4, Sp1, and YB1 directly bound to the GC boxes of the proximal Klf4 promoter. Upon RARα agonist stimulation, RARα was recruited to the Klf4 promoter through its interaction with KLF4, Sp1, and YB1 to form a transcriptional activation complex on the three GC boxes of the Klf4 promoter. These results suggest that RARα serves as an essential co-activator for ATRA signaling and that the recruitment of RARα to the KLF4-Sp1-YB1 complex, which leads to Klf4 expression in VSMCs, is independent of a retinoic acid response element. |
| Databáze: | OpenAIRE |
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