PT - JOURNAL ARTICLE AU - Nicolas Lonfat AU - Su Wang AU - ChangHee Lee AU - Jiho Choi AU - Peter J. Park AU - Connie Cepko TI - Otx2 and Oc1 directly regulate the transcriptional program of cone photoreceptor development AID - 10.1101/2020.06.29.177428 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.29.177428 4099 - http://biorxiv.org/content/early/2020/06/29/2020.06.29.177428.short 4100 - http://biorxiv.org/content/early/2020/06/29/2020.06.29.177428.full AB - The vertebrate retina is a highly organized structure of approximately 110 cell types. Retinal progenitor cells (RPCs) produce these cell types in a temporal order that is highly conserved. While some RPCs produce many cell types, some terminally dividing RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). Here, we compared the transcriptomes and chromatin profiles of such a restricted cone/HC RPC with those of other RPCs. We identified many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. We then showed that Otx2 and Oc1 directly regulate the activity of multiple CRMs genome-wide, including near genes important for cone development, such as Rxrg and Neurod1. In addition, we found that Otx2 regulates itself. These results suggest that Otx2 and Oc1 have a broader role than previously appreciated, and deepen our understanding of retinal development, which may benefit therapies for retinal diseases.Competing Interest StatementThe authors have declared no competing interest.