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PLoS Genet. 2014 Jul 3;10(7):e1004446. doi: 10.1371/journal.pgen.1004446. eCollection 2014 Jul.

DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.

Author information

1
Department of Botany and Plant Sciences, Center for Plant Cell Biology, Institute of Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America; ChemGen IGERT program, Center for Plant Cell Biology, Institute of Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America.
2
Department of Botany and Plant Sciences, Center for Plant Cell Biology, Institute of Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America.
3
Department of Botany and Plant Sciences, Center for Plant Cell Biology, Institute of Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America; School of Life Sciences, Lanzhou University, Lanzhou, China.
4
Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
5
Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.
6
Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America.
7
Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
8
Department of Botany and Plant Sciences, Center for Plant Cell Biology, Institute of Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America; Howard Hughes Medical Institute, University of California Riverside, Riverside, California, United States of America.

Abstract

RNA-directed DNA methylation (RdDM) and histone H3 lysine 9 dimethylation (H3K9me2) are related transcriptional silencing mechanisms that target transposable elements (TEs) and repeats to maintain genome stability in plants. RdDM is mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti-cancer properties that targets DNA topoisomerase 1α (TOP1α) was able to de-repress LUCL by reducing its DNA methylation and H3K9me2 levels. Further studies with Arabidopsis top1α mutants showed that TOP1α silences endogenous RdDM loci by facilitating the production of Pol V-dependent long non-coding RNAs, AGONAUTE4 recruitment and H3K9me2 deposition at TEs and repeats. This study assigned a new role in epigenetic silencing to an enzyme that affects DNA topology.

PMID:
24992598
PMCID:
PMC4080997
DOI:
10.1371/journal.pgen.1004446
[Indexed for MEDLINE]
Free PMC Article

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