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Unique activities of two overlapping PAX6 retinal enhancers

Uttley, K; Papanastasiou, AS; Lahne, M; Brisbane, JM; MacDonald, RB; Bickmore, WA; Bhatia, S; (2023) Unique activities of two overlapping PAX6 retinal enhancers. Life science alliance , 6 (11) , Article e202302126. 10.26508/lsa.202302126. (In press). Green open access

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Abstract

Enhancers play a critical role in development by precisely modulating spatial, temporal, and cell type-specific gene expression. Sequence variants in enhancers have been implicated in diseases; however, establishing the functional consequences of these variants is challenging because of a lack of understanding of precise cell types and developmental stages where the enhancers are normally active. PAX6 is the master regulator of eye development, with a regulatory landscape containing multiple enhancers driving the expression in the eye. Whether these enhancers perform additive, redundant or distinct functions is unknown. Here, we describe the precise cell types and regulatory activity of two PAX6 retinal enhancers, HS5 and NRE. Using a unique combination of live imaging and single-cell RNA sequencing in dual enhancer-reporter zebrafish embryos, we uncover differences in the spatiotemporal activity of these enhancers. Our results show that although overlapping, these enhancers have distinct activities in different cell types and therefore likely nonredundant functions. This work demonstrates that unique cell type-specific activities can be uncovered for apparently similar enhancers when investigated at high resolution in vivo.

Type: Article
Title: Unique activities of two overlapping PAX6 retinal enhancers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.26508/lsa.202302126
Publisher version: http://doi.org/10.26508/lsa.202302126
Language: English
Additional information: © 2023 Uttley et al. This article is available under a Creative Commons Licence (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Keywords: Animals, Regulatory Sequences, Nucleic Acid, Retina, Zebrafish, PAX6 Transcription Factor, Zebrafish Proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10176483
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