Disruption of RNAPII transcription elongation links Oncogenic splicing factor mutations to replciation stress and targetable alterations in chromatin landscape [TT-TL seq]

To investigate how whether the RNAPII defect is premature pause release defect or gene body elongation defect due to splicing factor mutations, we peformed TT-TL-seq (TT seq with a time lapse component) in K562 cells (wild type and SF3B1K700E mutant; U2AF1wild type vs U2AF1 S34F mutant) at 4 days after mutant allele expression We then performed metaplot-based and gene expression analysis using data obtained from TT-TL seq 5-min 4sU pulse in K562 (SF3B1 wild type vs SF3B1K700E mutant) as well as (U2AF1wild type vs U2AF1 S34F mutant) cells at 4 days, post doxycycline induction