Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1.
In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-04-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000386&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850183054527561728 |
|---|---|
| author | Michael Opel David Lando Carolina Bonilla Sarah C Trewick Abdelhalim Boukaba Julian Walfridsson James Cauwood Petra J H Werler Antony M Carr Tony Kouzarides Natalia V Murzina Robin C Allshire Karl Ekwall Ernest D Laue |
| author_facet | Michael Opel David Lando Carolina Bonilla Sarah C Trewick Abdelhalim Boukaba Julian Walfridsson James Cauwood Petra J H Werler Antony M Carr Tony Kouzarides Natalia V Murzina Robin C Allshire Karl Ekwall Ernest D Laue |
| author_sort | Michael Opel |
| collection | DOAJ |
| description | In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1(+) gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1Delta strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression. |
| format | Article |
| id | doaj-art-cc439e5abb7d4151ada48e31c7e1eea4 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2007-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-cc439e5abb7d4151ada48e31c7e1eea42025-08-20T02:17:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-04-0124e38610.1371/journal.pone.0000386Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1.Michael OpelDavid LandoCarolina BonillaSarah C TrewickAbdelhalim BoukabaJulian WalfridssonJames CauwoodPetra J H WerlerAntony M CarrTony KouzaridesNatalia V MurzinaRobin C AllshireKarl EkwallErnest D LaueIn order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1(+) gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1Delta strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000386&type=printable |
| spellingShingle | Michael Opel David Lando Carolina Bonilla Sarah C Trewick Abdelhalim Boukaba Julian Walfridsson James Cauwood Petra J H Werler Antony M Carr Tony Kouzarides Natalia V Murzina Robin C Allshire Karl Ekwall Ernest D Laue Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. PLoS ONE |
| title | Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. |
| title_full | Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. |
| title_fullStr | Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. |
| title_full_unstemmed | Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. |
| title_short | Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. |
| title_sort | genome wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian lsd1 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000386&type=printable |
| work_keys_str_mv | AT michaelopel genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT davidlando genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT carolinabonilla genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT sarahctrewick genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT abdelhalimboukaba genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT julianwalfridsson genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT jamescauwood genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT petrajhwerler genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT antonymcarr genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT tonykouzarides genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT nataliavmurzina genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT robincallshire genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT karlekwall genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 AT ernestdlaue genomewidestudiesofhistonedemethylationcatalysedbythefissionyeasthomologuesofmammalianlsd1 |