Abstract
In plants, the histone H3.1 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX RELATED PROTEIN 5 and 6 (ATXR5/6) regulate heterochromatic DNA replication and genome stability. Our initial studies showed that ATXR5/6 discriminate between histone H3 variants and preferentially methylate K27 on H3.1. In this study, we report three regulatory mechanisms contributing to the specificity of ATXR5/6. First, we show that ATXR5 preferentially methylates the R/F-K∗-S/C-G/A-P/C motif with striking preference for hydrophobic and aromatic residues in positions flanking this core of five amino acids. Second, we demonstrate that posttranscriptional modifications of residues neighboring K27 that are typically associated with actively transcribed chromatin are detrimental to ATXR5 activity. Third, we show that ATXR5 PHD domain employs a narrow binding pocket to selectively recognize unmethylated K4 of histone H3. Finally, we demonstrate that deletion or mutation of the PHD domain reduces the catalytic efficiency (kcat/Km of AdoMet) of ATXR5 up to 58-fold, highlighting themultifunctional nature of ATXR5 PHD domain. Overall, our results suggest that several molecular determinants regulate ATXR5/6 methyltransferase activity and epigenetic inheritance of H3.1 K27me1 mark in plants.
Original language | English (US) |
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Pages (from-to) | 6375-6387 |
Number of pages | 13 |
Journal | Nucleic acids research |
Volume | 45 |
Issue number | 11 |
DOIs | |
State | Published - Jun 1 2017 |
ASJC Scopus subject areas
- Genetics
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Dive into the research topics of 'Molecular basis for the methylation specificity of ATXR5 for histone H3'. Together they form a unique fingerprint.Datasets
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Crystal Structure of ATXR5 SET domain in complex with K36me3 histone H3 peptide
Bergamin, E. (Contributor), Sarvan, S. (Contributor), Malette, J. (Contributor), Eram, M. S. (Contributor), Sylvain, Y. (Contributor), Mongeon, V. (Contributor), Joshi, M. (Contributor), Brunzelle, J. S. (Contributor), Michaels, S. D. (Contributor), Blais, A. (Contributor), Vedadi, M. (Contributor) & Couture, J.-F. (Contributor), Protein Data Bank (PDB), Apr 19 2017
DOI: 10.2210/pdb5VAC/pdb, https://www.wwpdb.org/pdb?id=pdb_00005vac
Dataset
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Crystal structure of ATXR5 SET domain in complex with histone H3 di-methylated on R26
Bergamin, E. (Contributor), Sarvan, S. (Contributor), Malette, J. (Contributor), Eram, M. S. (Contributor), Sylvain, Y. (Contributor), Mongeon, V. (Contributor), Joshi, M. (Contributor), Brunzelle, J. S. (Contributor), Michaels, S. D. (Contributor), Blais, A. (Contributor), Vedadi, M. (Contributor) & Couture, J.-F. (Contributor), Protein Data Bank (PDB), Apr 5 2017
DOI: 10.2210/pdb5VAH/pdb, https://www.wwpdb.org/pdb?id=pdb_00005vah
Dataset
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CRYSTAL STRUCTURE OF ATXR5 IN COMPLEX WITH HISTONE H3.1 MONO-METHYLATED ON R26
Bergamin, E. (Contributor), Sarvan, S. (Contributor), Malette, J. (Contributor), Eram, M. S. (Contributor), Sylvain, Y. (Contributor), Mongeon, V. (Contributor), Joshi, M. (Contributor), Brunzelle, J. S. (Contributor), Michaels, S. D. (Contributor), Blais, A. (Contributor), Vedadi, M. (Contributor) & Couture, J.-F. (Contributor), Protein Data Bank (PDB), Apr 19 2017
DOI: 10.2210/pdb5VA6/pdb, https://www.wwpdb.org/pdb?id=pdb_00005va6
Dataset