Pathogenic variants in <i>CRX</i> have distinct <i>cis</i>-regulatory effects on enhancers and silencers in photoreceptors.

ABSTRACT: Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (CRX) are linked with human blinding diseases that vary in their severity and age of onset. How different variants in this single TF alter its function in ways that lead to a range of phenotypes is unclear. We characterized the effects of human disease-causing variants on CRX cis-regulatory function by deploying massively parallel reporter assays (MPRAs) in mouse retina explants 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 in these mutant Crx retinas corresponds with their phenotypic severity. The two variants affect similar sets of enhancer

SUBMITTER: Shepherdson JL 

PROVIDER: S-EPMC10984388 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature