{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE196nnn/GSE196618/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196618"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Synthetic transcription factor overrides persistent repressive chromatin marks [RNA-seq]","description":"The prevailing paradigms of epigenetic control posit that signature patterns of post-translational marks on histones guide specific transcriptional outcomes. Methylation of lysine-9 residue of histone H3 (H3K9me3) is implicated in transcriptional silencing through chromatin condensation by its reader HP-1 proteins. Erosion, erasure and subsequent replacement of H3K9me3 by active acetyl-lysine marks accompanies transcriptional up-regulation. Here, we report that a synthetic transcription elongation factor (SynTEF1), selectively targets the disease-causing GAA repeat expansion in frataxin and stimulates gene expression without erasure of the signature repressive marks or removal of HP1 proteins. Added epigenetic perturbation with a pharmacological agent leads to supra-synergistic frataxin expression that is unexpectedly accompanied by a dramatic rise in H3K9me3 levels. Active placement of the signature repressive mark is readily overridden by SynTEF1, demonstrating the fluidity and context-dependence of these marks in regulating gene expression. While forcing a reconsideration of how signature epigenetic marks are interpreted, our results provide key insights for therapeutic intervention in rationally reconfiguring disease-associated epigenetic states.","dates":{"publication":"2026/07/02"},"accession":"GSE196618","cross_references":{"GSM":["GSM5896918","GSM5896917","GSM5896916","GSM5896927","GSM5896926","GSM5896925","GSM5896924","GSM5896923","GSM5896922","GSM5896921","GSM5896920","GSM5896919"],"GPL":["16791"],"GSE":["196618"],"taxon":["Homo sapiens"]}}