Frøkjær-Jensen Christian, Jain Nimit, Hansen Loren, Davis M Wayne, Li Yongbin, Zhao Di, Rebora Karine, Millet Jonathan R M, Liu Xiao, Kim Stuart K, Dupuy Denis, Jorgensen Erik M, Fire Andrew Z
Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Biomedical Sciences and Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, 2200 Copenhagen N, Denmark.
Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2016 Jul 14;166(2):343-357. doi: 10.1016/j.cell.2016.05.072. Epub 2016 Jun 30.
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-base pair 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.
细胞从沉默外源遗传元件中获益，但必须同时避免使内源基因失活。尽管染色质修饰和RNA有助于维持沉默状态，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，我们证明了秀丽隐杆线虫中一种普遍存在的非编码DNA特征，其特点是具有10个碱基对的周期性An/Tn簇（PATC），可以使转基因在抑制性染色质结构域内进行生殖系表达。含有天然或合成PATC的转基因在生殖系中对位置效应斑驳和随机沉默具有抗性。在内源基因中，随着直系同源基因在进化过程中从活跃染色质转移到抑制性染色质，内含子长度和PATC特征会发生显著变化，这表明An/Tn周期性具有动态特征。我们提出，PATC构成了细胞免疫系统的基础，在异染色质环境中将某些内源基因识别为特权基因，而外源DNA可以被抑制，无需细胞对先前暴露的记忆。
