Zhang Xiaoyu, Yazaki Junshi, Sundaresan Ambika, Cokus Shawn, Chan Simon W-L, Chen Huaming, Henderson Ian R, Shinn Paul, Pellegrini Matteo, Jacobsen Steve E, Ecker Joseph R
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Cell. 2006 Sep 22;126(6):1189-201. doi: 10.1016/j.cell.2006.08.003. Epub 2006 Aug 31.
Cytosine methylation is important for transposon silencing and epigenetic regulation of endogenous genes, although the extent to which this DNA modification functions to regulate the genome is still unknown. Here we report the first comprehensive DNA methylation map of an entire genome, at 35 base pair resolution, using the flowering plant Arabidopsis thaliana as a model. We find that pericentromeric heterochromatin, repetitive sequences, and regions producing small interfering RNAs are heavily methylated. Unexpectedly, over one-third of expressed genes contain methylation within transcribed regions, whereas only approximately 5% of genes show methylation within promoter regions. Interestingly, genes methylated in transcribed regions are highly expressed and constitutively active, whereas promoter-methylated genes show a greater degree of tissue-specific expression. Whole-genome tiling-array transcriptional profiling of DNA methyltransferase null mutants identified hundreds of genes and intergenic noncoding RNAs with altered expression levels, many of which may be epigenetically controlled by DNA methylation.
胞嘧啶甲基化对于转座子沉默和内源基因的表观遗传调控至关重要,尽管这种DNA修饰在调节基因组中发挥作用的程度仍不清楚。在此,我们以开花植物拟南芥为模型,报告了首张全基因组的综合DNA甲基化图谱,分辨率为35个碱基对。我们发现,着丝粒周围的异染色质、重复序列以及产生小干扰RNA的区域高度甲基化。出乎意料的是,超过三分之一的表达基因在转录区域内含有甲基化,而只有约5%的基因在启动子区域显示甲基化。有趣的是,在转录区域甲基化的基因高度表达且组成型活跃,而启动子甲基化的基因表现出更高程度的组织特异性表达。对DNA甲基转移酶缺失突变体进行全基因组平铺阵列转录谱分析,鉴定出数百个表达水平改变的基因和基因间非编码RNA,其中许多可能受DNA甲基化的表观遗传控制。