Molecular basis for the methylation specificity of ATXR5 for histone H3

Elisa Bergamin, Sabina Sarvan, Josee Malette, Mohammad S. Eram, Yeung Sylvain, Vanessa Mongeon, Monika Joshi, Joseph S. Brunzelle, Scott D. Michaels, Alexandre Blais, Masoud Vedadi, Jean Francois Couture*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 languageEnglish (US)
Pages (from-to)6375-6387
Number of pages13
JournalNucleic acids research
Volume45
Issue number11
DOIs
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Molecular basis for the methylation specificity of ATXR5 for histone H3'. Together they form a unique fingerprint.

Cite this