{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Shepherdson JL"],"funding":["NEI NIH HHS","NHGRI NIH HHS","NIGMS NIH HHS"],"pubmed_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 <i>cis</i>-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"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.05.27.542576"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10245955"],"repository":["biostudies-literature"],"pubmed_title":["Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors."],"pmcid":["PMC10245955"],"funding_grant_id":["F30 EY033640","R01 GM121755","R01 EY012543","R01 EY032136","P30 EY002687","R01 EY027784","F31 HG011431"],"pubmed_authors":["Shepherdson JL","Zheng Y","Granas DM","Friedman RZ","Cohen BA","Sun C","White MA","Chen S","Oh IY"],"additional_accession":[]},"is_claimable":false,"name":"Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.","description":"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 <i>cis</i>-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","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-06-25T03:16:15.89Z","creation":"2025-04-19T14:14:27.85Z"},"accession":"S-EPMC10245955","cross_references":{"pubmed":["37292699"],"doi":["10.1101/2023.05.27.542576"]}}