{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Malachowski T"],"funding":["NSF","New York Stem Cell Foundation","NICHD NIH HHS","NIDA NIH HHS","NIMH NIH HHS","Blavatnik Family Foundation","National Institutes of Health","Chan Zuckerberg Initiative","NIMH","NIDDK NIH HHS","NINDS NIH HHS","NIDA","NIDDK","NIGMS NIH HHS"],"pagination":["5840-5858.e36"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10794044"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["186(26)"],"pubmed_abstract":["Short tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X chromosome in FXS patient-derived iPSCs, iPSC-derived neural progenitors, EBV-transformed lymphoblasts, and brain tissue with mutation-length CGG expansion. H3K9me3 domains connect via inter-chromosomal interactions and demarcate severe misfolding of TADs and loops. They harbor long synaptic genes replicating at the end of S phase, replication-stress-induced double-strand breaks, and STRs prone to stepwise somatic instability. CRISPR engineering of the mutation-length CGG to premutation"],"journal":["Cell"],"pubmed_title":["Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome."],"pmcid":["PMC10794044"],"funding_grant_id":["R37 MH120269","F300HD098015","DP1 MH129957","U01 DK127405","R35 GM128903","F30 HD098015","F31NS129317","R01 MH120269","F31 NS129317","U01 DA052715"],"pubmed_authors":["Ge C","Zhou L","Su C","Nguyen SC","Titus KR","Chandradoss KR","Pham K","Phillips-Cremins JE","Malachowski T","Wallace O","Joyce EF","Gong W","Wu H","Haws SA","Ryu HS","Boya R","Rojas LA","Kim JH","Cook AL","Luppino JM"],"additional_accession":[]},"is_claimable":false,"name":"Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome.","description":"Short tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X chromosome in FXS patient-derived iPSCs, iPSC-derived neural progenitors, EBV-transformed lymphoblasts, and brain tissue with mutation-length CGG expansion. H3K9me3 domains connect via inter-chromosomal interactions and demarcate severe misfolding of TADs and loops. They harbor long synaptic genes replicating at the end of S phase, replication-stress-induced double-strand breaks, and STRs prone to stepwise somatic instability. CRISPR engineering of the mutation-length CGG to premutation","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-05-20T03:12:40.466Z","creation":"2025-04-06T22:14:27.286Z"},"accession":"S-EPMC10794044","cross_references":{"pubmed":["38134876"],"doi":["10.1016/j.cell.2023.11.019"]}}