GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE196nnn/GSE196617/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196617GEOGSEfalseSynthetic transcription factor overrides persistent repressive chromatin marks [ChIP-seq]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.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 sapiens