LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription

摘要: Abstract FACT (facilitates chromatin transcription) is a protein complex that allows RNAPII to overcome the nucleosome-induced barrier transcription. While abundant in undifferentiated cells and many cancers, not or absent most tissues. Therefore, we screened for additional proteins might replace upon differentiation. Here report identification of two such proteins, LEDGF HDGF2, each containing HMGA-like AT-hooks PWWP methyl-lysine reading domain known bind H3K36me2 H3K36me3. HDGF2 localize with H3K36me2/3 at genomic regions active genes, usually adjacent H3K27me3 domains. In myoblasts, where expression low, are enriched on genes. Upon differentiation myotubes, levels decrease across genome while maintained. Moreover, recruited majority myotube up-regulated genes required their proper expression. knockout myoblasts exhibit an accumulation paused proximal first nucleosome within transcribed region target indicating defect early elongation. We propose substitute differentiated tissues distribution helps maintain transcriptional programs unique particular cell types. One Sentence Summary Chromatin bound allow block