GSE117155
LEDGF and HDGF2, histone H3K36 methyl-binding proteins that assist RNA polymerase II transcription through nucleosomes
FACT (facilitates chromatin transcription) is a protein complex that allows RNAPII to overcome the nucleosome-induced barrier to transcription.  While abundant in stem cells and many cancer cells, FACT it is not very abundant in most tissues.  Therefore, we screened for additional factors that might replace FACT in such tissues.  Here we report the identification of two such proteins, LEDGF and HDGF2, each containing two HMGA-like AT-hooks and a PWWP methyl-lysine reading domain known to bind to H3K36me2 and H3K36me3.  LEDGF and HDGF2 localize with H3K36me2/3 at genomic regions containing active genes, usually adjacent to H3K27me3 domains.  In myoblasts, where FACT expression is low, LEDGF and HDGF2 are enriched on most active genes.  Upon differentiation to myotubes, HDGF2 is recruited to the majority of myotube up-regulated genes and is required for their expression.  We propose that LEDGF and HDGF2 substitute for FACT in differentiated tissues and that their distribution on the genome helps maintain transcriptional programs unique to particular cell types. Overall design: Characterization of two new proteins having FACT-like activity ChIP-seq and RNA-Seq for studying the role of LEDGF and HDGF2 in 293TRex and two differentiation systems PRO-Seq of WT, HDGF2KO, and 'HDGF2KO rescued by WT' myoblast cells