{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Riccardi F"],"funding":["Telethon"],"pagination":["e0298965"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11146744"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(6)"],"pubmed_abstract":["Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongatio"],"journal":["PloS one"],"pubmed_title":["Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure."],"pmcid":["PMC11146744"],"funding_grant_id":["GGP17006"],"pubmed_authors":["Riccardi F","Pagani F","Romano G","Licastro D"],"additional_accession":[]},"is_claimable":false,"name":"Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.","description":"Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongatio","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-03T04:31:59.056Z","creation":"2026-04-24T03:09:53.042Z"},"accession":"S-EPMC11146744","cross_references":{"pubmed":["38829854"],"doi":["10.1371/journal.pone.0298965"]}}