Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice
<p>Abstract</p> <p>Background</p> <p>Etoposide (epipodophyllotoxin) is a chemical commonly used as an anti-cancer drug which inhibits DNA synthesis by blocking topoisomerase II activity. Previous studies in animal cells have demonstrated that etoposide constitutes a gen...
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BMC
2012-04-01
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| Series: | BMC Plant Biology |
| Online Access: | http://www.biomedcentral.com/1471-2229/12/48 |
| _version_ | 1819147553158987776 |
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| author | Yang Xuejiao Yu Yingjie Jiang Lily Lin Xiuyun Zhang Chunyu Ou Xiufang Osabe Kenji Liu Bao |
| author_facet | Yang Xuejiao Yu Yingjie Jiang Lily Lin Xiuyun Zhang Chunyu Ou Xiufang Osabe Kenji Liu Bao |
| author_sort | Yang Xuejiao |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Etoposide (epipodophyllotoxin) is a chemical commonly used as an anti-cancer drug which inhibits DNA synthesis by blocking topoisomerase II activity. Previous studies in animal cells have demonstrated that etoposide constitutes a genotoxic stress which may induce genomic instability including mobilization of normally quiescent transposable elements (TEs). However, it remained unknown whether similar genetically mutagenic effects could be imposed by etoposide in plant cells. Also, no information is available with regard to whether the drug may cause a perturbation of epigenetic stability in any organism.</p> <p>Results</p> <p>To investigate whether etoposide could generate genetic and/or epigenetic instability in plant cells, we applied etoposide to germinating seeds of six cultivated rice (<it>Oryza sativa</it> L.) genotypes including both subspecies, <it>japonica</it> and <it>indica</it>. Based on the methylation-sensitive gel-blotting results, epigenetic changes in DNA methylation of three TEs (<it>Tos17</it>, <it>Osr23</it> and <it>Osr36</it>) and two protein-encoding genes (<it>Homeobox</it> and <it>CDPK-related</it> genes) were detected in the etoposide-treated plants (S0 generation) in four of the six studied <it>japonica</it> cultivars, Nipponbare, RZ1, RZ2, and RZ35, but not in the rest <it>japonica</it> cultivar (Matsumae) and the <it>indica</it> cultivar (93-11). DNA methylation changes in the etoposide-treated S0 rice plants were validated by bisulfite sequencing at both of two analyzed loci (<it>Tos17</it> and <it>Osr36</it>). Transpositional activity was tested for eight TEs endogenous to the rice genome in both the S0 plants and their selfed progenies (S1 and S2) of one of the cultivars, RZ1, which manifested heritable phenotypic variations. Results indicated that no transposition occurred in the etoposide-treated S0 plants for any of the TEs. Nonetheless, a MITE transposon, <it>mPing</it>, showed rampant mobilization in the S1 and S2 progenies descended from the drug-treated S0 plants.</p> <p>Conclusions</p> <p>Our results demonstrate that etoposide imposes a similar genotoxic stress on plant cells as it does on animal and human cells, which may induce transgenerational genomic instability by instigating transpositional activation of otherwise dormant TEs. In addition, we show for the first time that etoposide may induce epigenetic instability in the form of altered DNA methylation patterns in eukaryotes. However, penetrance of the genotoxic effects of etoposide on plant cells, as being reflected as genetic and epigenetic instability, appears to be in a strictly genotype- and/or generation-dependent manner.</p> |
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| spelling | doaj.art-813c44b206e44680bd5627e9fff3d5012022-12-21T18:24:10ZengBMCBMC Plant Biology1471-22292012-04-011214810.1186/1471-2229-12-48Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in riceYang XuejiaoYu YingjieJiang LilyLin XiuyunZhang ChunyuOu XiufangOsabe KenjiLiu Bao<p>Abstract</p> <p>Background</p> <p>Etoposide (epipodophyllotoxin) is a chemical commonly used as an anti-cancer drug which inhibits DNA synthesis by blocking topoisomerase II activity. Previous studies in animal cells have demonstrated that etoposide constitutes a genotoxic stress which may induce genomic instability including mobilization of normally quiescent transposable elements (TEs). However, it remained unknown whether similar genetically mutagenic effects could be imposed by etoposide in plant cells. Also, no information is available with regard to whether the drug may cause a perturbation of epigenetic stability in any organism.</p> <p>Results</p> <p>To investigate whether etoposide could generate genetic and/or epigenetic instability in plant cells, we applied etoposide to germinating seeds of six cultivated rice (<it>Oryza sativa</it> L.) genotypes including both subspecies, <it>japonica</it> and <it>indica</it>. Based on the methylation-sensitive gel-blotting results, epigenetic changes in DNA methylation of three TEs (<it>Tos17</it>, <it>Osr23</it> and <it>Osr36</it>) and two protein-encoding genes (<it>Homeobox</it> and <it>CDPK-related</it> genes) were detected in the etoposide-treated plants (S0 generation) in four of the six studied <it>japonica</it> cultivars, Nipponbare, RZ1, RZ2, and RZ35, but not in the rest <it>japonica</it> cultivar (Matsumae) and the <it>indica</it> cultivar (93-11). DNA methylation changes in the etoposide-treated S0 rice plants were validated by bisulfite sequencing at both of two analyzed loci (<it>Tos17</it> and <it>Osr36</it>). Transpositional activity was tested for eight TEs endogenous to the rice genome in both the S0 plants and their selfed progenies (S1 and S2) of one of the cultivars, RZ1, which manifested heritable phenotypic variations. Results indicated that no transposition occurred in the etoposide-treated S0 plants for any of the TEs. Nonetheless, a MITE transposon, <it>mPing</it>, showed rampant mobilization in the S1 and S2 progenies descended from the drug-treated S0 plants.</p> <p>Conclusions</p> <p>Our results demonstrate that etoposide imposes a similar genotoxic stress on plant cells as it does on animal and human cells, which may induce transgenerational genomic instability by instigating transpositional activation of otherwise dormant TEs. In addition, we show for the first time that etoposide may induce epigenetic instability in the form of altered DNA methylation patterns in eukaryotes. However, penetrance of the genotoxic effects of etoposide on plant cells, as being reflected as genetic and epigenetic instability, appears to be in a strictly genotype- and/or generation-dependent manner.</p>http://www.biomedcentral.com/1471-2229/12/48 |
| spellingShingle | Yang Xuejiao Yu Yingjie Jiang Lily Lin Xiuyun Zhang Chunyu Ou Xiufang Osabe Kenji Liu Bao Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice BMC Plant Biology |
| title | Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice |
| title_full | Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice |
| title_fullStr | Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice |
| title_full_unstemmed | Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice |
| title_short | Changes in DNA methylation and transgenerational mobilization of a transposable element (<it>mPing</it>) by the Topoisomerase II inhibitor, Etoposide, in rice |
| title_sort | changes in dna methylation and transgenerational mobilization of a transposable element it mping it by the topoisomerase ii inhibitor etoposide in rice |
| url | http://www.biomedcentral.com/1471-2229/12/48 |
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