title: An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline.
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.
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Frøkjær-Jensen
authors.affiliation: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Nimit
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Loren
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Davis
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: IECB, University of Bordeaux, Laboratoire ARNA-INSERM, U869, 33600 Pessac, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Rebora
authors.affiliation: IECB, University of Bordeaux, Laboratoire ARNA-INSERM, U869, 33600 Pessac, France.
authors.forename: Jonathan R M
authors.initials: JRM
authors.lastname: Millet
authors.affiliation: Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: IECB, University of Bordeaux, Laboratoire ARNA-INSERM, U869, 33600 Pessac, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Dupuy
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jorgensen@biology.utah.edu.
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: afire@stanford.edu.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
mesh_terms: D000818:Animals; D001482:Base Composition; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin; D004251:DNA Transposable Elements; D021901:DNA, Intergenic / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D020868:Gene Silencing; D005854:Germ Cells / Q000378:metabolism; D007438:Introns; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019076:Transgenes
chemical_list: D002843:Chromatin; D004251:DNA Transposable Elements; D021901:DNA, Intergenic; D004279:DNA, Viral; D016372:RNA, Antisense; D012333:RNA, Messenger