An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline

• Published in: Cell 2016-07, Vol.166 (2), p.343-357
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Animals; Base Composition; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Chromatin; DNA Transposable Elements; DNA, Intergenic - metabolism; DNA, Viral - genetics; Gene Silencing; Germ Cells - metabolism; Introns; Promoter Regions, Genetic; RNA, Antisense - metabolism; RNA, Messenger - metabolism; Transgenes
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2016.05.072

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. [Display omitted] •Periodic, non-coding DNA can prevent transgenes from stochastic silencing in germline•Non-coding content of genes is shaped by genomic context and heterochromatin domains•Conditioning of active DNA may allow cells to distinguish foreign from host genes 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.