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Cell. 2016 Jul 14;166(2):343-357. doi: 10.1016/j.cell.2016.05.072. Epub 2016 Jun 30.

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

Author information

1
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.
2
Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
4
Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA.
5
School of Life Sciences, Tsinghua University, Beijing 100084, China.
6
IECB, University of Bordeaux, Laboratoire ARNA-INSERM, U869, 33600 Pessac, France.
7
Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA; School of Life Sciences, Tsinghua University, Beijing 100084, China.
8
Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
9
Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jorgensen@biology.utah.edu.
10
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: afire@stanford.edu.

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 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.

PMID:
27374334
PMCID:
PMC4947018
DOI:
10.1016/j.cell.2016.05.072
[Indexed for MEDLINE]
Free PMC Article

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