| First Author | Laursen KB | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 30 | Pages | 11891-11900 |
| PubMed ID | 29848550 | Mgi Jnum | J:267106 |
| Mgi Id | MGI:6197398 | Doi | 10.1074/jbc.RA118.001951 |
| Citation | Laursen KB, et al. (2018) Combinatorial knockout of RARalpha, RARbeta, and RARgamma completely abrogates transcriptional responses to retinoic acid in murine embryonic stem cells. J Biol Chem 293(30):11891-11900 |
| abstractText | All-trans-retinoic acid (RA), a potent inducer of cellular differentiation, functions as a ligand for retinoic acid receptors (RARalpha, beta, and gamma). RARs are activated by ligand binding, which induces transcription of direct genomic targets. However, whether embryonic stem cells respond to RA through routes that do not involve RARs is unknown. Here, we used CRISPR technology to introduce biallelic frameshift mutations in RARalpha, RARbeta, and RARgamma, thereby abrogating all RAR functions in murine embryonic stem cells. We then evaluated RA-responsiveness of the RAR-null cells using RNA-Seq transcriptome analysis. We found that the RAR-null cells display no changes in transcripts in response to RA, demonstrating that the RARs are essential for the regulation of all transcripts in murine embryonic stem cells in response to RA. Our key finding, that in embryonic stem cells the transcriptional effects of RA all depend on RARs, addresses a long-standing topic of discussion in the field of retinoic acid signaling. |
