RT Journal Article
SR Electronic
T1 <em>Rho</em> enhancers play unexpectedly minor roles in <em>Rhodopsin</em> transcription and rod cell integrity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.02.518920
DO 10.1101/2022.12.02.518920
A1 Sun, Chi
A1 Ruzycki, Philip A.
A1 Chen, Shiming
YR 2022
UL http://biorxiv.org/content/early/2022/12/02/2022.12.02.518920.abstract
AB Enhancers function with a basal promoter to control the transcription of target genes. Enhancer regulatory activity is often studied using reporter-based transgene assays. However, unmatched results have been reported when selected enhancers are silenced in situ. In this study, using genomic deletion analysis in mice, we investigated the roles of two previously identified enhancers and the promoter of the Rho gene that codes for the visual pigment rhodopsin. The Rho gene is robustly expressed by rod photoreceptors of the retina, and essential for the subcellular structure and visual function of rod photoreceptors. Mutations in RHO cause severe vision loss in humans. We found that each Rho regulatory region can independently mediate local epigenomic changes, but only the promoter is absolutely required for establishing active Rho chromatin configuration and transcription and maintaining the cell integrity and function of rod photoreceptors. To our surprise, two Rho enhancers that enable strong promoter activation in reporter assays are largely dispensable for Rho expression in vivo. Only small and age-dependent impact is detectable when both enhancers are deleted. Our results demonstrate context-dependent roles of enhancers and highlight the importance of studying functions of cis-regulatory regions in the native genomic context.Competing Interest StatementThe authors have declared no competing interest.