This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maksakova, I. A.
Right arrow Articles by Mager, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maksakova, I. A.
Right arrow Articles by Mager, D. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2009, p. 2456-2468, Vol. 29, No. 9
0270-7306/09/$08.00+0     doi:10.1128/MCB.01383-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Preferential Epigenetic Suppression of the Autonomous MusD over the Nonautonomous ETn Mouse Retrotransposons{triangledown} ,{dagger}

Irina A. Maksakova,{ddagger} Ying Zhang, and Dixie L. Mager*

Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada, and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

Received 2 September 2008/ Returned for modification 19 October 2008/ Accepted 15 February 2009

Nonautonomous retrotransposon subfamilies are often amplified in preference to their coding-competent relatives. However, the mechanisms responsible for such replicative success are poorly understood. Here, we demonstrate that the autonomous MusD long terminal repeat (LTR) retrotransposons are subject to greater epigenetic silencing than their nonautonomous cousins, the early transposons (ETns), which are expressed at a 170-fold-higher level than MusD in mouse embryonic stem (ES) cells. We show that, in ES cells, 5' LTRs and the downstream region of MusD elements are more heavily methylated and are associated with less-activating and more-repressive histone modifications than the highly similar ETnII sequences. The internal region of MusD likely contributes to their silencing, as transgenes with MusD, compared to those with ETnII sequences, show reduced reporter gene expression and a higher level of repressive histone marks. Genomic distribution patterns of MusD and ETn elements are consistent with stronger selection against MusD elements within introns, suggesting that MusD-associated silencing marks can negatively impact genes. We propose a model in which nonautonomous retrotransposons may gain transcriptional and retrotranspositional advantages over their coding-competent counterparts by elimination of the CpG-rich retroviral sequence targeting the autonomous subfamilies for silencing.

* Corresponding author. Mailing address: Terry Fox Laboratory, B.C. Cancer Agency, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada. Phone: (604) 675-8139. Fax: (604) 877-0712. E-mail: dmager{at}bccrc.ca

{triangledown} Published ahead of print on 9 March 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Medical Genetics, Life Sciences Institute, UBC, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.

Molecular and Cellular Biology, May 2009, p. 2456-2468, Vol. 29, No. 9
0270-7306/09/$08.00+0     doi:10.1128/MCB.01383-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»