Department of Integrated Genetics, National Institute of Genetics, Mishima, Shizuoka, Japan.
EMBO J. 2010 Oct 20;29(20):3496-506. doi: 10.1038/emboj.2010.227. Epub 2010 Sep 10.
In diverse eukaryotes, constitutively silent sequences, such as transposons and repeats, are marked by methylation at histone H3 lysine 9 (H3K9me). Although selective H3K9me is critical for maintaining genome integrity, mechanisms to exclude H3K9me from active genes remain largely unexplored. Here, we show in Arabidopsis that the exclusion depends on a histone demethylase gene, IBM1 (increase in BONSAI methylation). Loss-of-function ibm1 mutation results in ectopic H3K9me and non-CG methylation in thousands of genes. The ibm1-induced genic H3K9me depends on both histone methylase KYP/SUVH4 and DNA methylase CMT3, suggesting interdependence of two epigenetic marks--H3K9me and non-CG methylation. Notably, IBM1 enhances loss of H3K9me in transcriptionally de-repressed sequences. Furthermore, disruption of transcription in genes induces ectopic non-CG methylation, which mimics the loss of IBM1 function. We propose that active chromatin is stabilized by an autocatalytic loop of transcription and H3K9 demethylation. This process counteracts a similarly autocatalytic accumulation of silent epigenetic marks, H3K9me and non-CG methylation.
在不同的真核生物中，组成型沉默序列，如转座子和重复序列，通过组蛋白 H3 赖氨酸 9（H3K9me）的甲基化来标记。尽管选择性 H3K9me 对于维持基因组完整性至关重要，但将 H3K9me 排除在活性基因之外的机制在很大程度上仍未得到探索。在这里，我们在拟南芥中表明，这种排除依赖于一个组蛋白去甲基化酶基因 IBM1（增加 BONSAI 甲基化）。ibm1 功能丧失突变导致数千个基因中出现异位 H3K9me 和非 CG 甲基化。ibm1 诱导的基因 H3K9me 既依赖于组蛋白甲基转移酶 KYP/SUVH4，也依赖于 DNA 甲基转移酶 CMT3，表明两种表观遗传标记——H3K9me 和非 CG 甲基化之间存在相互依赖性。值得注意的是，IBM1 增强了转录去抑制序列中 H3K9me 的丢失。此外，基因中转录的中断会诱导异位非 CG 甲基化，这模拟了 IBM1 功能的丧失。我们提出，活性染色质通过转录和 H3K9 去甲基化的自动催化循环得到稳定。这个过程与沉默的表观遗传标记（H3K9me 和非 CG 甲基化）的类似自动催化积累相抗衡。
