| First Author | Perez-Cervantes C | Year | 2020 |
| Journal | Development | Volume | 147 |
| Issue | 3 | PubMed ID | 31915147 |
| Mgi Jnum | J:293534 | Mgi Id | MGI:6453593 |
| Doi | 10.1242/dev.184432 | Citation | Perez-Cervantes C, et al. (2020) Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types. Development 147(3):dev184432 |
| abstractText | Identification of cell type-specific cis-regulatory elements (CREs) is crucial for understanding development and disease, although identification of functional regulatory elements remains challenging. We hypothesized that context-specific CREs could be identified by context-specific non-coding RNA (ncRNA) profiling, based on the observation that active CREs produce ncRNAs. We applied ncRNA profiling to identify rod and cone photoreceptor CREs from wild-type and mutant mouse retinas, defined by presence or absence, respectively, of the rod-specific transcription factor (TF) Nrl Nrl-dependent ncRNA expression strongly correlated with epigenetic profiles of rod and cone photoreceptors, identified thousands of candidate rod- and cone-specific CREs, and identified motifs for rod- and cone-specific TFs. Colocalization of NRL and the retinal TF CRX correlated with rod-specific ncRNA expression, whereas CRX alone favored cone-specific ncRNA expression, providing quantitative evidence that heterotypic TF interactions distinguish cell type-specific CRE activity. We validated the activity of novel Nrl-dependent ncRNA-defined CREs in developing cones. This work supports differential ncRNA profiling as a platform for the identification of cell type-specific CREs and the discovery of molecular mechanisms underlying TF-dependent CRE activity. |
