Intact nucleosomal context enables chromodomain reader MRG15 to distinguish H3K36me3 from -me2
| Autor: | Brian Josephson, Sarah Faulkner, Fumiko Esashi, Tom Watts, Anthony M. Couturier, Benjamin G. Davis |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences 050208 finance 05 social sciences Lysine Context (language use) Peptide Chromodomain 03 medical and health sciences chemistry.chemical_compound Histone H3 0302 clinical medicine chemistry Docking (molecular) 030220 oncology & carcinogenesis 0502 economics and business Biophysics Nucleosome Epigenetics 050207 economics DNA 030304 developmental biology |
| Popis: | A wealth ofin vivoevidence 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 vitrostudies 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|