RT Journal Article
SR Electronic
T1 LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 500926
DO 10.1101/500926
A1 Gary LeRoy
A1 Ozgur Oksuz
A1 Nicolas Descostes
A1 Yuki Aoi
A1 Rais A. Ganai
A1 Havva Ortabozkoyun Kara
A1 Jia-Ray Yu
A1 Chul-Hwan Lee
A1 James Stafford
A1 Ali Shilatifard
A1 Danny Reinberg
YR 2018
UL http://biorxiv.org/content/early/2018/12/19/500926.abstract
AB FACT (facilitates chromatin transcription) is a protein complex that allows RNAPII to overcome the nucleosome-induced barrier to transcription. While abundant in undifferentiated cells and many cancers, FACT is not abundant or is absent in most tissues. Therefore, we screened for additional proteins that might replace FACT upon differentiation. 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, LEDGF levels decrease across the genome while HDGF2 levels are maintained. Moreover, HDGF2 is recruited to the majority of myotube up-regulated genes and is required for their proper expression. HDGF2 knockout myoblasts exhibit an accumulation of paused RNAPII proximal to the first nucleosome within the transcribed region of many HDGF2 target genes, indicating a defect in early elongation. 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.One Sentence Summary Chromatin bound LEDGF and HDGF2 proteins allow RNAPII to overcome the nucleosome-induced block to transcription.