Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase
Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase
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DOI：
10.1038/nature731
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发表时间：
2002-04-04
期刊：
影响因子：
64.8
通讯作者：
Jacobsen, SE
中科院分区：
文献类型：
--
作者：
Jackson, JP;Lindroth, AM;Jacobsen, SE
真核生物中的基因沉默与异染色质的形成有关，异染色质是一种阻止转录的蛋白质和DNA复合物。异染色质的特征在于DNA的胞嘧啶核苷酸的甲基化、组蛋白H3在赖氨酸9（H3 Lys 9）处的甲基化以及异染色质蛋白1（HP 1）与甲基化的H3 Lys 9的特异性结合（参考文献1-7）。虽然这些染色质修饰之间的关系通常是未知的，但在真菌粗糙脉孢菌中，DNA甲基化在H3 Lys 9甲基化的遗传下游起作用（8）。在这里，我们报告的分离KRYPTONITE，甲基转移酶基因特异性H3赖氨酸9，在突变体筛选中确定的基因沉默的抑制子在拟南芥SUPERMAN（NATURAL）基因座。功能丧失型氪石等位基因类似于DNA甲基转移酶基因染色体甲基化酶3（CMT 3）（9）中的突变体，显示出CpNpG三核苷酸位点（其中N为A、C、G或T）胞嘧啶甲基化的丧失和内源性逆转录转座子序列的再激活。我们表明，CMT 3与拟南芥同源的HP 1，这反过来又与甲基化组蛋白相互作用。这些数据表明，CpNpG DNA甲基化由组蛋白H3 Lys 9甲基化控制，通过CMT 3与甲基化染色质的相互作用。
Gene silencing in eukaryotes is associated with the formation of heterochromatin, a complex of proteins and DNA that block transcription. Heterochromatin is characterized by the methylation of cytosine nucleotides of the DNA, the methylation of histone H3 at lysine 9 (H3 Lys 9), and the specific binding of heterochromatin protein 1 (HP1) to methylated H3 Lys 9 (refs 1-7). Although the relationship between these chromatin modifications is generally unknown, in the fungus Neurospora crassa, DNA methylation acts genetically downstream of H3 Lys 9 methylation(8). Here we report the isolation of KRYPTONITE, a methyltransferase gene specific to H3 Lys 9, identified in a mutant screen for suppressors of gene silencing at the Arabidopsis thaliana SUPERMAN (SUP) locus. Loss-of-function kryptonite alleles resemble mutants in the DNA methyltransferase gene CHROMOMETHYLASE3 (CMT3)(9), showing loss of cytosine methylation at sites of CpNpG trinucleotides (where N is A, C, G or T) and reactivation of endogenous retrotransposon sequences. We show that CMT3 interacts with an Arabidopsis homologue of HP1, which in turn interacts with methylated histones. These data suggest that CpNpG DNA methylation is controlled by histone H3 Lys 9 methylation, through interaction of CMT3 with methylated chromatin.