Intact nucleosomal context enables chromodomain reader MRG15 to distinguish H3K36me3 from -me2
Faulkner, S.; Couturier, A. M.; Josephson, B.; Watts, T.; Davis, B. G.; Esashi, F.
Show abstract
A wealth of in vivo evidence demonstrates the physiological importance of histone H3 trimethylation at lysine 36 (H3K36me3), to which chromodomain-containing proteins, such as MRG15, bind preferentially compared to their dimethyl (H3K36me2) counterparts. However, in vitro studies using isolated H3 peptides have failed to recapitulate a causal interaction. Here, we show that MRG15 can clearly discriminate between synthetic, fully intact model nucleosomes containing H3K36me2 and H3K36me3. MRG15 docking studies, along with experimental observations and nucleosome structure analysis suggest a model where the H3K36 side chain is sequestered in intact nucleosomes via a hydrogen bonding interaction with the DNA backbone, which is abrogated when the third methyl group is added to form H3K36me3. Hence, this mechanism provides a methyl-switch for contextdependent reader selectivity. These results highlight the importance of such intra-chromatin interactions in understanding epigenetic regulation, a feature which is absent in commonly-used peptide or histone-only models.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.