Transcription elongation defects link oncogenic splicing factor mutations to targetable alterations in chromatin landscape.
Prajwal C BodduAbhishek GuptaRahul RoyBarbara De La Pena AvalosAne Olazabal HerreroNils NeuenkirchenJosh ZimmerNamrata ChandhokDarren KingYashuhito NannyaSeishi OgawaHaifan LinMatthew D SimonEloise DrayGary KupferAmit K VermaKarla M NeugebauerManoj M PillaiPublished in: bioRxiv : the preprint server for biology (2023)
Oncogenic mutations of SF3B1 and U2AF1 cause a gene-body RNAPII elongation defectRNAPII transcription elongation defect leads to transcription replication conflicts, DNA damage response, and changes to chromatin organization and H3K4me3 marksThe transcription elongation defect is linked to disruption of the early spliceosome formation through impaired interaction of HTATSF1 with mutant SF3B1.Changes to chromatin organization reveal potential therapeutic strategies by targeting the Sin3/HDAC pathway.