Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms

Rita Rebollo, Mohammad M. Karimi, Misha Bilenky, Liane Gagnier, Katharine Miceli-Royer, Ying Zhang, Preeti Goyal, Thomas M. Keane, Steven Jones, Martin Hirst, Matthew C. Lorincz, Dixie L. Mager

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The "arms race" relationship between transposable elements (TEs) and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE-induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES) cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements) at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness.

Original languageEnglish
Article numbere1002301
JournalPLoS Genetics
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

Fingerprint

Retroelements
Heterochromatin
retrotransposons
heterochromatin
DNA Transposable Elements
polymorphism
transposons
genetic polymorphism
gene
mice
cell lines
Cell Line
Genes
Intracisternal A-Particle Genes
arms race
DNA
genes
methylation
embryonic stem cells
DNA methylation

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Rebollo, R., Karimi, M. M., Bilenky, M., Gagnier, L., Miceli-Royer, K., Zhang, Y., ... Mager, D. L. (2011). Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. PLoS Genetics, 7(9), [e1002301]. https://doi.org/10.1371/journal.pgen.1002301

Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. / Rebollo, Rita; Karimi, Mohammad M.; Bilenky, Misha; Gagnier, Liane; Miceli-Royer, Katharine; Zhang, Ying; Goyal, Preeti; Keane, Thomas M.; Jones, Steven; Hirst, Martin; Lorincz, Matthew C.; Mager, Dixie L.

In: PLoS Genetics, Vol. 7, No. 9, e1002301, 09.2011.

Research output: Contribution to journalArticle

Rebollo, R, Karimi, MM, Bilenky, M, Gagnier, L, Miceli-Royer, K, Zhang, Y, Goyal, P, Keane, TM, Jones, S, Hirst, M, Lorincz, MC & Mager, DL 2011, 'Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms', PLoS Genetics, vol. 7, no. 9, e1002301. https://doi.org/10.1371/journal.pgen.1002301
Rebollo, Rita ; Karimi, Mohammad M. ; Bilenky, Misha ; Gagnier, Liane ; Miceli-Royer, Katharine ; Zhang, Ying ; Goyal, Preeti ; Keane, Thomas M. ; Jones, Steven ; Hirst, Martin ; Lorincz, Matthew C. ; Mager, Dixie L. / Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. In: PLoS Genetics. 2011 ; Vol. 7, No. 9.
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