Autoimmunity in Arabidopsis <em>acd11</em> Is Mediated by Epigenetic Regulation of an Immune Receptor

Certain pathogens deliver effectors into plant cells to modify host protein targets and thereby suppress immunity. These target modifications can be detected by intracellular immune receptors, or Resistance (R) proteins, that trigger strong immune responses including localized host cell death. The accelerated cell death 11 (acd11) “lesion mimic” mutant of Arabidopsis thaliana exhibits autoimmune phenotypes such as constitutive defense responses and cell death without pathogen perception. ACD11 encodes a putative sphingosine transfer protein, but its precise role during these processes is unknown. In a screen for lazarus (laz) mutants that suppress acd11 death we identified two genes, LAZ2 and LAZ5. LAZ2 encodes the histone lysine methyltransferase SDG8, previously shown to epigenetically regulate flowering time via modification of histone 3 (H3). LAZ5 encodes an RPS4-like R-protein, defined by several dominant negative alleles. Microarray and chromatin immunoprecipitation analyses showed that LAZ2/SDG8 is required for LAZ5 expression and H3 lysine 36 trimethylation at LAZ5 chromatin to maintain a transcriptionally active state. We hypothesize that LAZ5 triggers cell death in the absence of ACD11, and that cell death in other lesion mimic mutants may also be caused by inappropriate activation of R genes. Moreover, SDG8 is required for basal and R protein-mediated pathogen resistance in Arabidopsis, revealing the importance of chromatin remodeling as a key process in plant innate immunity.部分病原菌会将效应蛋白（effector）输送至植物细胞内，以修饰宿主蛋白靶点，进而抑制宿主免疫。这类靶标修饰可被胞内免疫受体，即抗病（Resistance, R）蛋白所识别，进而触发包括宿主局部细胞死亡在内的强烈免疫应答。拟南芥（Arabidopsis thaliana）的加速细胞死亡11（accelerated cell death 11, acd11）“病斑模拟”突变体呈现出自体免疫表型，例如无需病原菌识别即可触发组成型防御响应与细胞死亡。ACD11编码一种推定的鞘氨醇转运蛋白（sphingosine transfer protein），但目前尚不明确其在上述过程中的具体功能。在筛选可抑制acd11细胞死亡的懒（lazarus, laz）突变体时，我们鉴定到两个基因LAZ2与LAZ5。LAZ2编码组蛋白赖氨酸甲基转移酶SDG8，此前研究表明该蛋白可通过修饰组蛋白3（histone 3, H3）表观调控开花时间。LAZ5编码一类类RPS4的抗病蛋白，已有研究通过若干显性负效等位基因对其进行了定义。基因芯片（Microarray）与染色质免疫沉淀（chromatin immunoprecipitation, ChIP）分析结果显示，LAZ2/SDG8对于LAZ5的表达以及LAZ5染色质区域的组蛋白3赖氨酸36三甲基化（H3 lysine 36 trimethylation）以维持转录活跃状态是必需的。我们提出假说：在ACD11缺失的情况下，LAZ5会触发细胞死亡；而其他病斑模拟突变体的细胞死亡，或许也由抗病基因的异常激活所导致。此外，在拟南芥中，SDG8对于基础免疫以及抗病蛋白介导的病原菌抗性均不可或缺，这揭示了染色质重塑作为植物先天免疫关键过程的重要性。