Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of any systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genomic instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared the effects of 5-azacytidine (AC), 2'-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective inhibitor of TGS was DAC, followed by DZNep, zebularine and AC. We confirmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps us to understand the function of DNA methylation in plants and opens the possibility of using epigenetic inhibitors in biotechnology.

Biogeosystem Modelling Group ING PAN Institute of Geological Sciences Polish Academy of Sciences Research Center in Krakow Senacka 1 PL 31 002 Krakow Poland

Biotechnology of Horticultural Crops TUM School of Life Sciences Weihenstephan Technical University of Munich Liesel Beckmann Straße 1 DE 85354 Freising Germany

Institute of Experimental Botany CZ 779 00 Olomouc Czech Republic

Institute of Organic Chemistry and Biochemistry CZ 166 10 Praha 6 Czech Republic

Leibniz Institute of Plant Genetics and Crop Plant Research Stadt Seeland DE 06466 Gatersleben OT Germany

Max Planck Institute for Plant Breeding Research DE 50829 Cologne Germany

The Polish Academy of Sciences The Franciszek Górski Institute of Plant Physiology Niezapominajek 21 PL 30 239 Krakow Poland

Unit of Botany and Plant Physiology Institute of Plant Biology and Biotechnology Faculty of Biotechnology and Horticulture University of Agriculture in Krakow Al 29 Listopada 54 PL 31 425 Krakow Poland

Zobrazit více v PubMed

Alberts, B. (2002) Chromosomal DNA and its packaging in the chromatin fiber. In Molecular Biology of the Cell (Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. eds). New York: Garland science.

van Attikum, H., Bundock, P., Overmeer, R.M., Lee, L., Gelvin, S.B. and Hooykaas, P.J.J. (2003) The Arabidopsis AtLIG4 gene is required for the repair of DNA damage, but not for the integration of Agrobacterium T-DNA. Nucleic Acids Res. 31, 4247-4255.

Aufsatz, W., Mette, M.F., van der Winden, J., Matzke, M. and Matzke, A.J.M. (2002) HDA6, a putative histone deacetylase needed to enhance DNA methylation induced by double-stranded RNA. EMBO J. 21, 6832-6841.

Baubec, T., Pecinka, A., Rozhon, W. and Mittelsten Scheid, O. (2009) Effective, homogeneous and transient interference with cytosine methylation in plant genomic DNA by zebularine. Plant J. 57, 542-554.

Baubec, T., Dinh, H.Q., Pecinka, A., Rakic, B., Rozhon, W., Wohlrab, B., von Haeseler, A. and Scheid, O.M. (2010) Cooperation of multiple chromatin modifications can generate unanticipated stability of epigenetic states in Arabidopsis. Plant Cell, 22, 34-47.

Baubec, T., Finke, A., Mittelsten Scheid, O. and Pecinka, A. (2014) Meristem-specific expression of epigenetic regulators safeguards transposon silencing in Arabidopsis. EMBO Rep. 15, 446-452.

Bewick, A.J., Ji, L. and Niederhuth, C.E. et al. (2016) On the origin and evolutionary consequences of gene body DNA methylation. Proc. Natl Acad. Sci. USA, 113, 9111-9116.

Bustin, S.A., Benes, V., Garson, J.A. et al. (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55: 611-622.

Champion, C., Guianvarc’h, D., Sénamaud-Beaufort, C., Jurkowska, R.Z., Jeltsch, A., Ponger, L., Arimondo, P.B. and Guieysse-Peugeot, A.-L. (2010) Mechanistic insights on the inhibition of C5 DNA methyltransferases by zebularine. PLoS ONE, 5, e12388.

Chang, S. and Pikaard, C.S. (2005) Transcript profiling in Arabidopsis reveals complex responses to global inhibition of DNA methylation and histone deacetylation. J. Biol. Chem. 280, 796-804.

Cho, S.-W., Ishii, T., Matsumoto, N., Tanaka, H., Eltayeb, A.E. and Tsujimoto, H. (2011) Effects of the cytidine analogue zebularine on wheat mitotic chromosomes. Chromosom. Sci. 14, 23-28.

Córdoba-Cañero, D., Dubois, E., Ariza, R.R., Doutriaux, M.-P. and Roldán-Arjona, T. (2010) Arabidopsis Uracil DNA glycosylase (UNG) is required for base excision repair of uracil and increases plant sensitivity to 5-fluorouracil. J. Biol. Chem. 285, 7475-7483.

Culligan, K.M., Robertson, C.E., Foreman, J., Doerner, P. and Britt, A.B. (2006) ATR and ATM play both distinct and additive roles in response to ionizing radiation. Plant J. 48, 947-961.

De Schutter, K., Joubès, J., Cools, T. et al. (2007) Arabidopsis WEE1 kinase controls cell cycle arrest in response to activation of the DNA integrity checkpoint. Plant Cell, 19, 211-225.

Diaz, M., Pecinkova, P., Nowicka, A., Baroux, C., Sakamoto, T., Yuliani Gandha, P., Jeřábková, H., Matsunaga, S., Grossniklaus, U. and Pecinka, A. (2019) SMC5/6 complex subunit NSE4A is involved in DNA damage repair and seed development in Arabidopsis. Plant Cell, 31, 1579-1597.

Döbel, P., Schubert, I. and Rieger, R. (1978) Distribution of heterochromatin in a reconstructed karyotype of Vicia faba as identified by banding- and DNA-late replication patterns. Chromosoma, 69, 193-209.

Du, J., Zhong, S. and Bernatavichute, Y.V. et al. (2012) Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell, 151, 167-180.

Elmayan, T., Proux, F. and Vaucheret, H. (2005) Arabidopsis RPA2: A genetic link among transcriptional gene silencing, DNA repair, and DNA replication. Curr. Biol. 15, 1919-1925.

Fajkus, J., Vyskot, B. and Bezděk, M. (1992) Changes in chromatin structure due to hypomethylation induced with 5-azacytidine or DL-ethionine. FEBS Lett. 314, 13-16.

Fauser, F., Schiml, S. and Puchta, H. (2014) Both CRISPR/Cas-based nucleases and nickases can be used efficiently for genome engineering in Arabidopsis thaliana. Plant J. 79, 348-359.

Feng, S., Jacobsen, S.E. and Reik, W. (2010) Epigenetic reprogramming in plant and animal development. Science, 330, 622-627.

Fidantsef, A.L., Mitchell, D.L. and Britt, A.B. (2000) The Arabidopsis UVH1 gene is a homolog of the yeast repair endonuclease RAD1. Plant Physiol. 124, 579-586.

Finke, A., Rozhon, W. and Pecinka, A. (2018) Analysis of DNA methylation content and patterns in plants. Methods Mol. Biol. 1694, 277-298.

Fiskus, W., Wang, Y. and Sreekumar, A. et al. (2009) Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood, 114, 2733-2743.

Foerster, A.M., Dinh, H.Q., Sedman, L., Wohlrab, B. and Mittelsten Scheid, O. (2011) Genetic rearrangements can modify chromatin features at epialleles. PLoS Genet. 7, e1002331.

Fojtová, M., Kovařík, A., Votruba, I. and Holý, A. (1998) Evaluation of the impact of S-adenosylhomocysteine metabolic pools on cytosine methylation of the tobacco genome. Eur. J. Biochem. 252, 347-352.

Fransz, P., Soppe, W. and Schubert, I. (2003) Heterochromatin in interphase nuclei of Arabidopsis thaliana. Chromosom. Res. 11, 227-240.

Fučík, V., Michaelis, A. and Rieger, R. (1970) On the induction of segment extension and chromatid structural changes in Vicia faba chromosomes after treatment with 5-azacytidine and 5-azadeoxycytidine. Mutat. Res. Mol. Mech. Mutagen. 9, 599-606.

Fulneček, J., Matyášek, R., Votruba, I., Holý, A., Křížová, K. and Kovařík, A. (2011) Inhibition of SAH-hydrolase activity during seed germination leads to deregulation of flowering genes and altered flower morphology in tobacco. Mol. Genet. Genomics, 285, 225-236.

Ghoshal, K., Datta, J., Majumder, S., Bai, S., Kutay, H., Motiwala, T. and Jacob, S.T. (2005) 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol. Cell. Biol. 25, 4727-4741.

Glazer, R.I., Knode, M.C., Tseng, C.K.H., Haines, D.R. and Marquez, V.E. (1986) 3-deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells. Biochem. Pharmacol. 35, 4523-4527.

Griffin, P.T., Niederhuth, C.E. and Schmitz, R.J. (2016). A comparative analysis of 5-azacytidine and zebularine induced DNA demethylation. G3: Genes - Genomes - Genetics, 6, 2773-2780.

Hegde, V., McFarlane, R.J., Taylor, E.M. and Price, C. (1996) The genetics of the repair of 5-azacytidine-mediated DNA damage in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 251, 483-492.

Herrmann, N.J., Knoll, A. and Puchta, H. (2015) The nuclease FAN1 is involved in DNA crosslink repair in Arabidopsis thaliana independently of the nuclease MUS81. Nucleic Acids Res. 43, 3653-3666.

Hu, Z., Cools, T. and De Veylder, L. (2016) Mechanisms used by plants to cope with DNA damage. Annu. Rev. Plant Biol. 67, 439-462.

Huettel, B., Kanno, T., Daxinger, L., Aufsatz, W., Matzke, A.J.M. and Matzke, M. (2006) Endogenous targets of RNA-directed DNA methylation and Pol IV in Arabidopsis. EMBO J. 25, 2828-2836.

Jackson, J.P., Lindroth, A.M., Cao, X. and Jacobsen, S.E. (2002) Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature, 416, 556-560.

Kankel, M.W., Ramsey, D.E., Stokes, T.L., Flowers, S.K., Haag, J.R., Jeddeloh, J.A., Riddle, N.C., Verbsky, M.L. and Richards, E.J. (2003) Arabidopsis MET1 cytosine Methyltransferase mutants. Genetics, 163, 1109-1122.

Kawakatsu, T., Hwang, S.C. and Jupe, F., et al. (2016) Epigenomic diversity in a global collection of Arabidopsis thaliana accessions. Cell, 166, 492-505.

Kimura, S. and Sakaguchi, K. (2006) DNA repair in plants. Chem. Rev. 106, 753-766.

Kiziltepe, T., Hideshima, T. and Catley, L. et al. (2007) 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol. Cancer Ther. 6, 1718-1727.

Kovarik, A., Van Houdt, H., Holý, A. and Depicker, A. (2000) Drug-induced hypomethylation of a posttranscriptionally silenced transgene locus of tobacco leads to partial release of silencing. FEBS Lett. 467, 47-51.

Kuo, H.K., Griffith, J.D. and Kreuzer, K.N. (2007) 5-azacytidine-induced Methyltransferase-DNA adducts block DNA replication in vivo. Cancer Res. 67, 8248-8254.

Law, J.A. and Jacobsen, S.E. (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat. Rev. Genet. 11, 204-220.

Lister, R., O’Malley, R.C., Tonti-Filippini, J., Gregory, B.D., Berry, C.C., Millar, A.H. and Ecker, J.R. (2008) Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell, 133, 523-536.

Liu, C. and Weigel, D. (2015) Chromatin in 3D: progress and prospects for plants. Genome Biol. 16, 170.

Liu, C.-H., Finke, A., Diaz, M., Rozhon, W., Poppenberger, B., Baubec, T. and Pecinka, A. (2015) Repair of DNA damage induced by the cytidine analog zebularine requires ATR and ATM in Arabidopsis. Plant Cell, 27, 1788-1800.

Lyko, F. and Brown, R. (2005) DNA Methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Nat. Cancer Inst., 97, 1498-1506.

Mathieu, O., Reinders, J., Čaikovski, M., Smathajitt, C. and Paszkowski, J. (2007) Transgenerational stability of the Arabidopsis epigenome is coordinated by CG methylation. Cell, 130, 851-862.

Matoušová, M., Votruba, I., Otmar, M., Tloušťová, E., Günterová, J. and Mertlíková-Kaiserová, H. (2011) 2′-deoxy-5,6-dihydro-5-azacytidine-a less toxic alternative of 2′-deoxy-5-azacytidine: a comparative study of hypomethylating potential. Epigenetics, 6, 769-776.

Matzke, M.A. and Mosher, R.A. (2014) RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. Nat. Rev. Genet. 15, 394-408.

Meier, I., Richards, E.J. and Evans, D.E. (2017) Cell biology of the plant nucleus. Annu. Rev. Plant Biol. 68, 139-172.

Mengiste, T., Revenkova, E., Bechtold, N. and Paszkowski, J. (1999) An SMC-like protein is required for efficient homologous recombination in Arabidopsis. EMBO J. 18, 4505-4512.

Menolfi, D., Delamarre, A., Lengronne, A., Pasero, P. and Branzei, D. (2015) Essential roles of the Smc5/6 complex in replication through natural pausing sites and endogenous DNA damage tolerance. Mol. Cell, 60, 835-846.

Miranda, T.B., Cortez, C.C., Yoo, C.B., Liang, G., Abe, M., Kelly, T.K., Marquez, V.E. and Jones, P.A. (2009) DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol. Cancer Ther. 8, 1579-1588.

Mittelsten Scheid, O., Afsar, K. and Paszkowski, J. (1998) Release of epigenetic gene silencing by trans-acting mutations in Arabidopsis. Proc. Natl Acad. Sci. USA, 95, 632-637.

Moissiard, G., Cokus, S.J. and Cary, J. et al. (2012) MORC family ATPases required for heterochromatin condensation and gene silencing. Science, 336, 1448-1451.

Morel, J.-B., Mourrain, P., Béclin, C. and Vaucheret, H. (2000) DNA methylation and chromatin structure affect transcriptional and post-transcriptional transgene silencing in Arabidopsis. Curr. Biol. 10, 1591-1594.

Mynarzova, Z. and Baranek, M. (2015) An evaluation of the impact of demethylating agents treatment using TGS 16C Nicotiana benthamiana reporter line. MendelNet, 428-433.

Nowicka, A., Juzoń, K., Krzewska, M., Dziurka, M., Dubas, E., Kopeć, P., Zieliński, K. and Żur, I. (2019) Chemically-induced DNA de-methylation alters the effectiveness of microspore embryogenesis in triticale. Plant Sci. 287, 110189.

O’Malley, R.C., Barragan, C.C. and Ecker, J.R. (2015) A user’s guide to the Arabidopsis T-DNA insertional mutant collections. Methods Mol. Biol. (Clifton, N.J.), 1284, 323-342.

Orta, M.L., Höglund, A., Calderón-Montaño, J.M., Domínguez, I., Burgos-Morón, E., Visnes, T., Pastor, N., Ström, C., López-lázaro, M. and Helleday, T. (2014) The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2′-deoxycytidine lesions. Nucleic Acids Res. 42, 9108-9120.

Ossowski, S., Schwab, R. and Weigel, D. (2008) Gene silencing in plants using artificial microRNAs and other small RNAs. Plant J. 53, 674-690.

Pecinka, A. and Liu, C.-H. (2014) Drugs for plant chromosome and chromatin research. Cytogenet Genome Res. 143, 51-59.

Pecinka, A., Schubert, V., Meister, A., Kreth, G., Klatte, M., Lysak, M., Fuchs, J. and Schubert, I. (2004) Chromosome territory arrangement and homologous pairing in nuclei of Arabidopsis thaliana are predominantly random except for NOR-bearing chromosomes. Chromosoma, 113, 258-269.

Pecinka, A., Rosa, M., Schikora, A., Berlinger, M., Hirt, H., Luschnig, C. and Scheid, O.M. (2009) Transgenerational stress memory is not a general response in Arabidopsis. PLoS ONE, 4, e5202.

Pecinka, A., Dinh, H.Q., Baubec, T., Rosa, M., Lettner, N. and Scheid, O.M. (2010) Epigenetic regulation of repetitive elements is attenuated by prolonged heat stress in Arabidopsis. Plant Cell, 22, 3118-3129.

Probst, A.V., Fransz, P.F., Paszkowski, J. and Scheid, O.M. (2003) Two means of transcriptional reactivation within heterochromatin. Plant J. 33, 743-749.

Puchta, H., Swoboda, P. and Hohn, B. (1995) Induction of intrachromosomal homologous recombination in whole plants. Plant J. 7, 203-210.

Riha, K., Watson, J.M., Parkey, J. and Shippen, D.E. (2002) Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J. 21, 2819-2826.

Rocha, P.S.C.F., Sheikh, M., Melchiorre, R., Fagard, M., Boutet, S., Loach, R., Moffatt, B., Wagner, C., Vaucheret, H. and Furner, I. (2005) The Arabidopsis HOMOLOGY-DEPENDENT GENE SILENCING1 gene codes for an S-adenosyl-l-homocysteine hydrolase required for DNA methylation-dependent gene silencing. Plant Cell, 17, 404-417.

Rosa, S., Ntoukakis, V., Ohmido, N., Pendle, A., Abranches, R. and Shaw, P. (2014) Cell differentiation and development in Arabidopsis are associated with changes in histone dynamics at the single-cell level. Plant Cell, 26, 4821-4833.

Salem, A.M.H., Nakano, T., Takuwa, M., Matoba, N., Tsuboi, T., Terato, H., Yamamoto, K., Yamada, M., Nohmi, T. and Ide, H. (2009) Genetic analysis of repair and damage tolerance mechanisms for DNA-protein cross-links in Escherichia coli. J. Bacteriol. 191, 5657-5668.

Schiml, S., Fauser, F. and Puchta, H. (2016) Repair of adjacent single-strand breaks is often accompanied by the formation of tandem sequence duplications in plant genomes. Proc. Natl Acad. Sci. USA, 113, 7266-7271.

Solís, M.-T., El-Tantawy, A.-A., Cano, V., Risueño, M.C. and Testillano, P.S. (2015) 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley. Front. Plant Sci. 6, 472.

Soppe, W.J.J., Jasencakova, Z., Houben, A., Kakutani, T., Meister, A., Huang, M.S., Jacobsen, S.E., Schubert, I. and Fransz, P.F. (2002) DNA methylation controls histone H3 lysine 9 methylation and heterochromatin assembly in Arabidopsis. EMBO J. 21, 6549-6559.

Southern, E.M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98, 503-517.

Steimer, A., Amedeo, P., Afsar, K., Fransz, P., Scheid, O.M. and Paszkowski, J. (2000) Endogenous targets of transcriptional gene silencing in Arabidopsis. Plant Cell, 12, 1165-1178.

Stingele, J., Bellelli, R. and Boulton, S.J. (2017) Mechanisms of DNA-protein crosslink repair. Nat. Rev. Mol. Cell Biol. 18, 563.

Stroud, H., Greenberg, M.V.C., Feng, S., Bernatavichute, Y.V. and Jacobsen, S.E. (2013) Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell, 152, 352-364.

Takuno, S. and Gaut, B.S. (2012) Body-methylated genes in Arabidopsis thaliana are functionally important and evolve slowly. Mol. Biol. Evol. 29, 219-227.

Tanaka, M., Kikuchi, A. and Kamada, H. (2008) The Arabidopsis Histone deacetylases HDA6 and HDA19 contribute to the repression of embryonic properties after germination. Plant Physiol. 146, 149-161.

Venturelli, S., Belz, R.G. and Kämper, A., et al. (2015) Plants release precursors of Histone Deacetylase inhibitors to suppress growth of competitors. Plant Cell, 27, 3175-3189.

Watanabe, K., Pacher, M., Dukowic, S., Schubert, V., Puchta, H. and Schubert, I. (2009) The STRUCTURAL MAINTENANCE OF CHROMOSOMES 5/6 complex promotes sister chromatid alignment and homologous recombination after DNA damage in Arabidopsis thaliana. Plant Cell, 21, 2688-2699.

Xu, C.-R., Liu, C., Wang, Y.-L., Li, L.-C., Chen, W.-Q., Xu, Z.-H. and Bai, S.-N. (2005) Histone acetylation affects expression of cellular patterning genes in the Arabidopsis root epidermis. Proc. Natl Acad. Sci. USA, 102, 14469-14474.

Yoo, C.B. and Jones, P.A. (2006) Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug Discov. 5, 37-50.

Yoshiyama, K., Conklin, P.A., Huefner, N.D. and Britt, A.B. (2009) Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage. Proc. Natl Acad. Sci. USA, 106, 12843-12848.

Zadražil, S., Fučík, V., Bartl, P., Šormová, Z. and Šorm, F. (1965) The structure of DNA from Escherichia coli cultured in the presence of 5-azacytidine. Biochim. Biophys. Acta - Nucleic Acids Protein Synth. 108, 701-703.

Zemach, A., Kim, M.Y., Hsieh, P.-H., Coleman-Derr, D., Eshed-Williams, L., Thao, K., Harmer, S.L. and Zilberman, D. (2013) The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell, 153, 193-205.

Zilberman, D., Gehring, M., Tran, R.K., Ballinger, T. and Henikoff, S. (2007) Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat. Genet. 39, 61-69.

A Practical Approach to High-Throughput and Accurate Mapping-by-Sequencing in Arabidopsis

Exploring the crop epigenome: a comparison of DNA methylation profiling techniques

SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis

Effect of DNA methylation, modified by 5-azaC, on ecophysiological responses of a clonal plant to changing climate

Zebularine induces enzymatic DNA-protein crosslinks in 45S rDNA heterochromatin of Arabidopsis nuclei

Comparative proteomic analysis provides new insights into regulation of microspore embryogenesis induction in winter triticale (× Triticosecale Wittm.) after 5-azacytidine treatment

Insights into the Role of Transcriptional Gene Silencing in Response to Herbicide-Treatments in Arabidopsis thaliana

Transformed tissue of Dionaea muscipula J. Ellis as a source of biologically active phenolic compounds with bactericidal properties