The vertebrate retina is generated by retinal progenitor cells (RPCs), which produce >100 cell types. While some RPCs produce many cell types, other RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). We used genome-wide assays of chromatin structure to compare the profiles of a restricted cone/HC and those of other RPCs. These data nominated regions of regulatory activity, which were tested in tissue, leading to the identification of many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. Two transcription factors, Otx2 and Oc1, were found to bind to many of these CRMs, including those near genes important for cone development and function, and their binding sites were required for activity. We also found that Otx2 has a predicted autoregulatory CRM. These results suggest that Otx2, Oc1 and possibly other Onecut genes have a broad role in coordinating cone development and function. The many newly discovered CRMs for cones are potentially useful reagents for gene therapy of cone diseases.
Cis-regulatory dissection of cone development reveals a broad role for Otx2 and Oc transcription factors
These authors contributed equally
Currently Viewing Accepted Manuscript - Newer Version Available
Nicolas Lonfat, Su Wang, ChangHee Lee, Mauricio Garcia, Jiho Choi, Peter J. Park, Connie Cepko; Cis-regulatory dissection of cone development reveals a broad role for Otx2 and Oc transcription factors. Development 2021; dev.198549. doi: https://doi.org/10.1242/dev.198549
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