Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.

ABSTRACT: Dozens of variants in the photoreceptor-specific transcription factor (TF) CRX are linked with human blinding diseases that vary in their severity and age of onset. It is unclear how different variants in this single TF alter its function in ways that lead to a range of phenotypes. We examined the effects of human disease-causing variants on CRX cis-regulatory function by deploying massively parallel reporter assays (MPRAs) in live mouse retinas carrying knock-ins of two variants, one in the DNA binding domain (p.R90W) and the other in the transcriptional effector domain (p.E168d2). The degree of reporter gene dysregulation caused by the variants corresponds with their phenotypic severity. The two variants affect similar sets of enhancers, while p.E168d2 has stronger effects on sile

SUBMITTER: Shepherdson JL 

PROVIDER: S-EPMC10245955 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature