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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-1106v1 26/5/1166    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Minoguchi, S. Articles by Iba, H. PubMed PubMed Citation Articles by Minoguchi, S. Articles by Iba, H.

EMBRYONIC STEM CELLS

Instability of Retroviral DNA Methylation in Embryonic Stem Cells

Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Key Words. Embryonic stem cells • Epigenetics • Murine stem cell virus-based vector • Methylation

Correspondence: Hideo Iba, Ph.D., Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku Tokyo, 108-8639, Japan. Telephone: 81-3-5449-5730; Fax: 81-3-5449-5449; e-mail: iba{at}ims.u-tokyo.ac.jp

Received December 31, 2007; accepted for publication February 26, 2008.
First published online in STEM CELLS EXPRESS   March 6, 2008.



The epigenetic status of pluripotent stem cells has been demonstrated to be extremely unstable. In our current study, we have attempted to further investigate the epigenetic dynamics of the stem cell genome by monitoring the expression of the murine stem cell virus (MSCV) retroviral vector in embryonic stem (ES) cells. Although MSCV is progressively silenced by proviral DNA methylation in ES cells, a substantial number of MSCV-transduced ES cell clones do show variegated proviral expression. This expression profile is due in part to the transient and reversible properties of MSCV silencing. However, the spontaneous reactivation rates of the silenced proviruses differ significantly between these variegated clones, indicating that the reversibility of silencing is dependent on the proviral integration site. Our current data suggest that the fidelity of DNA methylation among the genomic sequences that flank the proviral integration sites may be the determinant of this reversibility of MSCV silencing. Given that the adjoining epigenome environment affects the epigenetic regulation of proviral DNA, the reversible MSCV silencing effect is thus likely to reflect a unique and interesting feature of ES cell epigenome regulation that has not previously been revealed.

Disclosure of potential conflicts of interest is found at the end of this article.