Genome-wide analysis of the cytosine methylation profile in Arabidopsis thaliana crown galls

Integration of the bacterial T-DNA into the plant genome by virulent agrobacteria causes crown gall development on many plant species. Plant tumor development shares fundamental similarities with mammalian cancer progression despite obvious differences in initiation of tumor development. For neoplastic growth in mammals, DNA methylation changes are known to be essential. The role of epigenetic modifications for plant tumor development is addressed here. Genome-wide comparison of methylation profiles of Arabidopsis crown galls and tumor-free tissue revealed 2,876 annotated genes that were affected by differential methylation. Thereof, 1,822 genes were hit by hypermethylated regions and 1,100 genes overlapped with hypomethylated regions (sum of hyper-and hypomethylated genes is higher than the number of affected genes because one gene may contain several differentially methylated regions [DMRs]). DMRs found to be methylated only in tumor-free tissue covered 275 kb of the genome, whereas those methylated only in crown galls total to 560 kb. Contrary to the globally hypermethylated tumor genome, promoter regions of protein coding genes appeared to be rather hypomethylated. In contrast, mammalian cancer cells are associated with global hypomethylation and local hypermethylation of gene promoters. In summary, while aberrant DNA methylation in mammals increases malignacy of the cancer phenotype, our results indicate that methylation events in the plant genome rather confine tumor growth. All 15,431 mCIP-enriched regions reported in the paper are contained in the supplementary BED files. mCIP of gDNA from crown galls vs. mCIP of gDNA from inflorescence stalks (3 biol. replicates each)

致病性农杆菌将细菌T-DNA（Transfer DNA）整合至植物基因组后，会在多种植物宿主上诱导冠瘿瘤的形成。尽管肿瘤发生的起始过程存在显著差异，但植物肿瘤的发生发展与哺乳动物癌症的进程具有诸多核心相似之处。已知DNA甲基化改变对于哺乳动物的肿瘤性生长至关重要。本研究聚焦于表观遗传修饰在植物肿瘤发生发展中的作用。通过对拟南芥冠瘿瘤与无瘤组织的全基因组甲基化谱进行比较分析，本研究共鉴定出2876个受差异甲基化影响的注释基因。其中，1822个基因受到高甲基化区域的影响，1100个基因则与低甲基化区域存在重叠（高、低甲基化基因的总数高于受影响基因的总数量，这是因为单个基因可能包含多个差异甲基化区域[Differentially Methylated Regions，DMRs]）。仅在无瘤组织中存在甲基化的DMRs覆盖了基因组的275千碱基对（kb），而仅在冠瘿瘤中存在甲基化的DMRs总覆盖长度达560千碱基对。与整体呈现高甲基化状态的肿瘤基因组不同，蛋白编码基因的启动子区域反而呈现低甲基化特征。与之形成鲜明对比的是，哺乳动物癌细胞的基因组整体呈现低甲基化状态，而基因启动子区域则呈现局部高甲基化特征。综上所述，尽管哺乳动物体内的异常DNA甲基化会增强癌症表型的恶性程度，但本研究结果表明，植物基因组中的甲基化事件反而会抑制肿瘤的生长。本论文中报道的全部15431个富集mCIP的区域均收录于补充的BED格式文件中。该实验比较了冠瘿瘤组织基因组DNA（genomic DNA，gDNA）的mCIP与花序轴组织基因组DNA的mCIP（每组均设置3次生物学重复）