This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Padjen, K. Articles by Storb, U. Search for Related Content PubMed PubMed Citation Articles by Padjen, K. Articles by Storb, U.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2005, p. 4782-4791, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4782-4791.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

DNA Methylation Precedes Chromatin Modifications under the Influence of the Strain-Specific Modifier Ssm1

Kristoffer Padjen, Sarayu Ratnam, and Ursula Storb^*

Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637

Received 9 February 2005/ Returned for modification 23 February 2005/ Accepted 3 March 2005

Ssm1 is responsible for the mouse strain-specific DNA methylation of the transgene HRD. In adult mice of the C57BL/6 (B6) strain, the transgene is methylated at essentially all CpGs. However, when the transgene is bred into the DBA/2 (D2) strain, it is almost completely unmethylated. Strain-specific methylation arises during differentiation of embryonic stem (ES) cells. Here we show that Ssm1 causes striking chromatin changes during the development of the early embryo in both strains. In undifferentiated ES cells of both strains, the transgene is in a chromatin state between active and inactive. These states are still observed 1 week after beginning ES cell differentiation. However, 4 weeks after initiating differentiation, in B6, the transgene has become heterochromatic, and in D2, the transgene has become euchromatic. HRD is always expressed in D2, but in B6, it is expressed only in early embryos. The transgene is already more methylated in B6 ES cells than in D2 ES cells and becomes increasingly methylated during development in B6, until essentially all CpGs in the critical guanosine phosphoribosyl transferase core are methylated. Clearly, DNA methylation of HRD precedes chromatin compaction and loss of expression, suggesting that the B6 form of Ssm1 interacts with DNA to cause strain-specific methylation that ultimately results in inactive chromatin.

---

* Corresponding author. Mailing address: University of Chicago, Department of Molecular Genetics and Cell Biology, 920 E. 58th St., Chicago, IL 60637. Phone: (773) 702-4440. Fax: (773) 702-3172. E-mail: stor{at}midway.uchicago.edu.

---

Molecular and Cellular Biology, June 2005, p. 4782-4791, Vol. 25, No. 11
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.11.4782-4791.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Bao-Cutrona, M., Moral, P. (2009). Unexpected Expression Pattern of Tetracycline-Regulated Transgenes in Mice. Genetics 181: 1687-1691 [Abstract] [Full Text]  
• Shen, H. M., Ratnam, S., Storb, U. (2005). Targeting of the Activation-Induced Cytosine Deaminase Is Strongly Influenced by the Sequence and Structure of the Targeted DNA. Mol. Cell. Biol. 25: 10815-10821 [Abstract] [Full Text]