Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana.
Eukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcrip...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-06-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4890748?pdf=render |
| _version_ | 1818409327988310016 |
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| author | Christopher J Hale Magdalena E Potok Jennifer Lopez Truman Do Ao Liu Javier Gallego-Bartolome Scott D Michaels Steven E Jacobsen |
| author_facet | Christopher J Hale Magdalena E Potok Jennifer Lopez Truman Do Ao Liu Javier Gallego-Bartolome Scott D Michaels Steven E Jacobsen |
| author_sort | Christopher J Hale |
| collection | DOAJ |
| description | Eukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcriptional upregulation of transposons, and a genome instability defect in which there is an accumulation of excess DNA corresponding to pericentromeric heterochromatin. We designed a forward genetic screen to identify suppressors of the atxr5/6 phenotype that uncovered loss-of-function mutations in two components of the TREX-2 complex (AtTHP1, AtSAC3B), a SUMO-interacting E3 ubiquitin ligase (AtSTUbL2) and a methyl-binding domain protein (AtMBD9). Additionally, using a reverse genetic approach, we show that a mutation in a plant homolog of the tumor suppressor gene BRCA1 enhances the atxr5/6 phenotype. Through characterization of these mutations, our results suggest models for the production atxr5 atxr6-induced extra DNA involving conflicts between the replicative and transcriptional processes in the cell, and suggest that the atxr5 atxr6 transcriptional defects may be the cause of the genome instability defects in the mutants. These findings highlight the critical intersection of transcriptional silencing and DNA replication in the maintenance of genome stability of heterochromatin. |
| first_indexed | 2024-12-14T09:57:52Z |
| format | Article |
| id | doaj.art-6685a86cac8248b5ab7a1e829208dec9 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T09:57:52Z |
| publishDate | 2016-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-6685a86cac8248b5ab7a1e829208dec92022-12-21T23:07:21ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-06-01126e100609210.1371/journal.pgen.1006092Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana.Christopher J HaleMagdalena E PotokJennifer LopezTruman DoAo LiuJavier Gallego-BartolomeScott D MichaelsSteven E JacobsenEukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcriptional upregulation of transposons, and a genome instability defect in which there is an accumulation of excess DNA corresponding to pericentromeric heterochromatin. We designed a forward genetic screen to identify suppressors of the atxr5/6 phenotype that uncovered loss-of-function mutations in two components of the TREX-2 complex (AtTHP1, AtSAC3B), a SUMO-interacting E3 ubiquitin ligase (AtSTUbL2) and a methyl-binding domain protein (AtMBD9). Additionally, using a reverse genetic approach, we show that a mutation in a plant homolog of the tumor suppressor gene BRCA1 enhances the atxr5/6 phenotype. Through characterization of these mutations, our results suggest models for the production atxr5 atxr6-induced extra DNA involving conflicts between the replicative and transcriptional processes in the cell, and suggest that the atxr5 atxr6 transcriptional defects may be the cause of the genome instability defects in the mutants. These findings highlight the critical intersection of transcriptional silencing and DNA replication in the maintenance of genome stability of heterochromatin.http://europepmc.org/articles/PMC4890748?pdf=render |
| spellingShingle | Christopher J Hale Magdalena E Potok Jennifer Lopez Truman Do Ao Liu Javier Gallego-Bartolome Scott D Michaels Steven E Jacobsen Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. PLoS Genetics |
| title | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. |
| title_full | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. |
| title_fullStr | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. |
| title_full_unstemmed | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. |
| title_short | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. |
| title_sort | identification of multiple proteins coupling transcriptional gene silencing to genome stability in arabidopsis thaliana |
| url | http://europepmc.org/articles/PMC4890748?pdf=render |
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