An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline.
An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline.
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DOI：
10.1016/j.cell.2016.05.072
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发表时间：
2016-07-14
期刊：
影响因子：
64.5
通讯作者：
Fire AZ
中科院分区：
文献类型：
--
作者：
Frøkjær-Jensen C;Jain N;Hansen L;Davis MW;Li Y;Zhao D;Rebora K;Millet JRM;Liu X;Kim SK;Dupuy D;Jorgensen EM;Fire AZ
细胞受益于沉默外来遗传元件，但必须同时避免使内源基因失活。虽然染色质修饰和RNA有助于沉默状态的维持，但沉默区域的建立将不可避免地反映潜在的DNA序列和/或结构。在这里，我们证明了一个普遍的非编码DNA功能的秀丽隐杆线虫，其特征在于由10个碱基对周期性的An/Tn簇（PATCs），可以许可转基因的生殖系表达内抑制染色质结构域。含有天然或合成PATCs的转基因对种系中的位置效应杂色和随机沉默具有抗性。在内源性基因中，内含子长度和PATC-字符经历了戏剧性的变化，直向同源物从活性到抑制染色质随着进化时间的推移，表明动态字符的An/Tn周期性。我们提出，PATCs形成的基础上的细胞免疫系统，识别某些内源性基因在异染色质的背景下，作为特权，而外来DNA可以被抑制，不需要细胞的记忆之前的曝光。非编码DNA序列模式可以防止生殖细胞中转基因的表观遗传沉默，揭示了大量非编码DNA的功能作用以及细胞识别和沉默外源DNA的可能机制
Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-basepair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the An/Tn periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure. A non-coding DNA sequence pattern can prevent epigenetic silencing of transgenes in germ cells, revealing a functional role for an abundant class of non-coding DNA and a possible mechanism by which cells may recognize and silence foreign DNA