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

Christian Frøkjær-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

doi:10.1016/j.cell.2016.05.072

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

Christian Frøkjær-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 journal › Article › peer-review

56 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 language	English (US)
Pages (from-to)	343-357
Number of pages	15
Journal	Cell
Volume	166
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2016.05.072
State	Published - Jul 14 2016
Externally published	Yes

Bibliographical note

Funding Information:
We thank J. Feldman, A. Villeneuve, S. Strome, A. Rechtsteiner, J. Lieb, K. Ikegami, C. Engert, S. Klemm, T. Machacek, V. Jantsch, C. Girard, G. Maro, D. Nix, the A.Z.F. and E.M.J. lab members, and K. Hoe for expert technical assistance. This work was supported by the Carlsberg Foundation (C.F.J.), Direktør Ib Henriksens Foundation (C.F.J.), a Stanford Graduate Fellowship (N.J.), NIH grants R01GM095817 (E.M.J) and R01GM37706 (A.Z.F.), and the Howard Hughes Medical Institute (E.M.J.).

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Access to Document

10.1016/j.cell.2016.05.072

Cite this

@article{6c01162238f84319b549a112c2b6b953,

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.",

author = "Christian Fr{\o}kj{\ae}r-Jensen and Nimit Jain and Loren Hansen and Davis, {M. Wayne} and Yongbin Li and Di Zhao and Karine Rebora and Millet, {Jonathan R R.M.} and Xiao Liu and Kim, {Stuart K.} and Denis Dupuy and Jorgensen, {Erik M.} and Fire, {Andrew Z.}",

note = "Funding Information: We thank J. Feldman, A. Villeneuve, S. Strome, A. Rechtsteiner, J. Lieb, K. Ikegami, C. Engert, S. Klemm, T. Machacek, V. Jantsch, C. Girard, G. Maro, D. Nix, the A.Z.F. and E.M.J. lab members, and K. Hoe for expert technical assistance. This work was supported by the Carlsberg Foundation (C.F.J.), Direkt{\o}r Ib Henriksens Foundation (C.F.J.), a Stanford Graduate Fellowship (N.J.), NIH grants R01GM095817 (E.M.J) and R01GM37706 (A.Z.F.), and the Howard Hughes Medical Institute (E.M.J.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

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doi = "10.1016/j.cell.2016.05.072",

language = "English (US)",

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AU - Frøkjær-Jensen, Christian

AU - Jain, Nimit

AU - Hansen, Loren

AU - Davis, M. Wayne

AU - Li, Yongbin

AU - Zhao, Di

AU - Rebora, Karine

AU - Millet, Jonathan R R.M.

AU - Liu, Xiao

AU - Kim, Stuart K.

AU - Dupuy, Denis

AU - Jorgensen, Erik M.

AU - Fire, Andrew Z.

N1 - Funding Information: We thank J. Feldman, A. Villeneuve, S. Strome, A. Rechtsteiner, J. Lieb, K. Ikegami, C. Engert, S. Klemm, T. Machacek, V. Jantsch, C. Girard, G. Maro, D. Nix, the A.Z.F. and E.M.J. lab members, and K. Hoe for expert technical assistance. This work was supported by the Carlsberg Foundation (C.F.J.), Direktør Ib Henriksens Foundation (C.F.J.), a Stanford Graduate Fellowship (N.J.), NIH grants R01GM095817 (E.M.J) and R01GM37706 (A.Z.F.), and the Howard Hughes Medical Institute (E.M.J.). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/7/14

Y1 - 2016/7/14

N2 - 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.

AB - 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.

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