Cargando…
Molecular basis for the methylation specificity of ATXR5 for histone H3
In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases 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 K...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499861/ https://www.ncbi.nlm.nih.gov/pubmed/28383693 http://dx.doi.org/10.1093/nar/gkx224 |
_version_ | 1783248542815485952 |
---|---|
author | Bergamin, Elisa Sarvan, Sabina Malette, Josée Eram, Mohammad S. Yeung, Sylvain Mongeon, Vanessa Joshi, Monika Brunzelle, Joseph S. Michaels, Scott D. Blais, Alexandre Vedadi, Masoud Couture, Jean-François |
author_facet | Bergamin, Elisa Sarvan, Sabina Malette, Josée Eram, Mohammad S. Yeung, Sylvain Mongeon, Vanessa Joshi, Monika Brunzelle, Joseph S. Michaels, Scott D. Blais, Alexandre Vedadi, Masoud Couture, Jean-François |
author_sort | Bergamin, Elisa |
collection | PubMed |
description | In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases 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 post-transcriptional 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 (k(cat)/K(m) of AdoMet) of ATXR5 up to 58-fold, highlighting the multifunctional 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. |
format | Online Article Text |
id | pubmed-5499861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54998612017-07-12 Molecular basis for the methylation specificity of ATXR5 for histone H3 Bergamin, Elisa Sarvan, Sabina Malette, Josée Eram, Mohammad S. Yeung, Sylvain Mongeon, Vanessa Joshi, Monika Brunzelle, Joseph S. Michaels, Scott D. Blais, Alexandre Vedadi, Masoud Couture, Jean-François Nucleic Acids Res Gene regulation, Chromatin and Epigenetics In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases 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 post-transcriptional 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 (k(cat)/K(m) of AdoMet) of ATXR5 up to 58-fold, highlighting the multifunctional 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. Oxford University Press 2017-06-20 2017-04-05 /pmc/articles/PMC5499861/ /pubmed/28383693 http://dx.doi.org/10.1093/nar/gkx224 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Bergamin, Elisa Sarvan, Sabina Malette, Josée Eram, Mohammad S. Yeung, Sylvain Mongeon, Vanessa Joshi, Monika Brunzelle, Joseph S. Michaels, Scott D. Blais, Alexandre Vedadi, Masoud Couture, Jean-François Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title | Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title_full | Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title_fullStr | Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title_full_unstemmed | Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title_short | Molecular basis for the methylation specificity of ATXR5 for histone H3 |
title_sort | molecular basis for the methylation specificity of atxr5 for histone h3 |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499861/ https://www.ncbi.nlm.nih.gov/pubmed/28383693 http://dx.doi.org/10.1093/nar/gkx224 |
work_keys_str_mv | AT bergaminelisa molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT sarvansabina molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT malettejosee molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT erammohammads molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT yeungsylvain molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT mongeonvanessa molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT joshimonika molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT brunzellejosephs molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT michaelsscottd molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT blaisalexandre molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT vedadimasoud molecularbasisforthemethylationspecificityofatxr5forhistoneh3 AT couturejeanfrancois molecularbasisforthemethylationspecificityofatxr5forhistoneh3 |