Catoni Marco, Griffiths Jayne, Becker Claude, Zabet Nicolae Radu, Bayon Carlos, Dapp Mélanie, Lieberman-Lazarovich Michal, Weigel Detlef, Paszkowski Jerzy
The Sainsbury Laboratory, University of Cambridge, Cambridge, UK.
Department of Plant Biology, University of Geneva, Geneva, Switzerland.
EMBO J. 2017 Mar 1;36(5):617-628. doi: 10.15252/embj.201695602. Epub 2017 Jan 9.
Transgenerationally heritable epialleles are defined by the stable propagation of alternative transcriptional states through mitotic and meiotic cell cycles. Given that the propagation of DNA methylation at CpG sites, mediated in by MET1, plays a central role in epigenetic inheritance, we examined genomewide DNA methylation in partial and complete loss-of-function mutants. We interpreted the data in relation to transgenerational epiallelic stability, which allowed us to classify chromosomal targets of epigenetic regulation into (i) single copy and methylated exclusively at CpGs, readily forming epialleles, and (ii) transposon-derived, methylated at all cytosines, which may or may not form epialleles. We provide evidence that DNA sequence features such as density of CpGs and genomic repetitiveness of the loci predispose their susceptibility to epiallelic switching. The importance and predictive power of these genetic features were confirmed by analyses of common epialleles in natural accessions, epigenetic recombinant inbred lines (epiRILs) and also verified in rice.
跨代遗传的表观等位基因是由交替转录状态通过有丝分裂和减数分裂细胞周期的稳定传播来定义的。鉴于由MET1介导的CpG位点的DNA甲基化传播在表观遗传中起着核心作用，我们研究了功能部分丧失和完全丧失的突变体的全基因组DNA甲基化情况。我们根据跨代表观等位基因的稳定性来解释数据，这使我们能够将表观遗传调控的染色体靶点分为两类：（i）单拷贝且仅在CpG处甲基化，易于形成表观等位基因；（ii）转座子衍生的，在所有胞嘧啶处甲基化，可能形成也可能不形成表观等位基因。我们提供的证据表明，诸如CpG密度和基因座的基因组重复性等DNA序列特征使其易于发生表观等位基因转换。通过对自然群体中的常见表观等位基因、表观遗传重组自交系（epiRILs）进行分析，并在水稻中得到验证，证实了这些遗传特征的重要性和预测能力。
