This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thorvaldsen, J. L.
Right arrow Articles by Bartolomei, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thorvaldsen, J. L.
Right arrow Articles by Bartolomei, M. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2006, p. 1245-1258, Vol. 26, No. 4
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.4.1245-1258.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Developmental Profile of H19 Differentially Methylated Domain (DMD) Deletion Alleles Reveals Multiple Roles of the DMD in Regulating Allelic Expression and DNA Methylation at the Imprinted H19/Igf2 Locus

Joanne L. Thorvaldsen, Andrew M. Fedoriw, Son Nguyen, and Marisa S. Bartolomei*

Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 28 September 2005/ Returned for modification 3 November 2005/ Accepted 25 November 2005

The differentially methylated domain (DMD) of the mouse H19 gene is a methylation-sensitive insulator that blocks access of the Igf2 gene to shared enhancers on the maternal allele and inactivates H19 expression on the methylated paternal allele. By analyzing H19 DMD deletion alleles H19{Delta}DMD and H19{Delta}3.8kb-5'H19 in pre- and postimplantation embryos, we show that the DMD exhibits positive transcriptional activity and is required for H19 expression in blastocysts and full activation of H19 during subsequent development. We also show that the DMD is required to establish Igf2 imprinting by blocking access to shared enhancers when Igf2 monoallelic expression is initiated in postimplantation embryos and that the single remaining CTCF site of the H19{Delta}DMD allele is unable to provide this function. Furthermore, our data demonstrate that sequence outside of the DMD can attract some paternal-allele-specific CpG methylation 5' of H19 in preimplantation embryos, although this methylation is not maintained during postimplantation in the absence of the DMD. Finally, we report a conditional allele floxing the 1.6-kb sequence deleted from the H19{Delta}DMD allele and demonstrate that the DMD is required to maintain repression of the maternal Igf2 allele and the full activity of the paternal Igf2 allele in neonatal liver.

* Corresponding author. Mailing address: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104. Phone: (215) 898-9063. Fax: (215) 573-6434. E-mail: bartolom{at}mail.med.upenn.edu.

Molecular and Cellular Biology, February 2006, p. 1245-1258, Vol. 26, No. 4
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.4.1245-1258.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Matsuzaki, H., Okamura, E., Shimotsuma, M., Fukamizu, A., Tanimoto, K. (2009). A Randomly Integrated Transgenic H19 Imprinting Control Region Acquires Methylation Imprinting Independently of Its Establishment in Germ Cells. Mol. Cell. Biol. 29: 4595-4603 [Abstract] [Full Text]  
  • Singh, V., Srivastava, M. (2008). Enhancer Blocking Activity of the Insulator at H19-ICR Is Independent of Chromatin Barrier Establishment. Mol. Cell. Biol. 28: 3767-3775 [Abstract] [Full Text]  
  • Verona, R. I., Thorvaldsen, J. L., Reese, K. J., Bartolomei, M. S. (2008). The Transcriptional Status but Not the Imprinting Control Region Determines Allele-Specific Histone Modifications at the Imprinted H19 Locus. Mol. Cell. Biol. 28: 71-82 [Abstract] [Full Text]  
  • Sparago, A., Russo, S., Cerrato, F., Ferraiuolo, S., Castorina, P., Selicorni, A., Schwienbacher, C., Negrini, M., Ferrero, G. B., Silengo, M. C., Anichini, C., Larizza, L., Riccio, A. (2007). Mechanisms causing imprinting defects in familial Beckwith-Wiedemann syndrome with Wilms' tumour. Hum Mol Genet 16: 254-264 [Abstract] [Full Text]  
  • Holmes, R., Chang, Y., Soloway, P. D. (2006). Timing and Sequence Requirements Defined for Embryonic Maintenance of Imprinted DNA Methylation at Rasgrf1. Mol. Cell. Biol. 26: 9564-9570 [Abstract] [Full Text]  
  • Engel, N., Thorvaldsen, J. L., Bartolomei, M. S. (2006). CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet 15: 2945-2954 [Abstract] [Full Text]  


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