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

Christian Froekjaer Jensen, Nimit Jain, Loren Hansen, M. Wayne Davis, Yongbin Li, Di Zhao, Karine Rebora, Jonathan R R.M. Millet, Xiao Liu, Stuart K. Kim, Denis Dupuy, Erik M. Jorgensen*, Andrew Z. Fire

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 A n /T n -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 A n /T n 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.

Original languageEnglish (US)
Pages (from-to)343-357
Number of pages15
JournalCell
Volume166
Issue number2
DOIs
StatePublished - Jul 14 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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