Human Molecular Genetics Advance Access published online on February 24, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl027
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute of Genetics and Biophysics ‘A. Buzzati Traverso’ CNR, Naples, Italy
* To whom correspondence should be addressed. Maintenance of X-inactivation is achieved through a combination of different repressive mechanisms, thus perpetuating the silencing message through many cell generations. The second human X-Y pseudoautosomal region 2 (PAR2) is a useful model to explore the features and internal relationships of the epigenetic circuits involved in this phenomenon. Recently, we demonstrated that DNA methylation plays an essential role for the maintenance of X- and Y-inactivation of the PAR2 gene SYBL1; here we report that the silencing of the second repressed PAR2 gene, SPRY3, appears to be independent of DNA methylation. In contrast to SYBL1, the inactive X and Y alleles of SPRY3 are not reactivated in cells treated with a DNA methylation inhibitor and in cells from ICF syndrome patients, which have mutations in the DNA methyltransferase gene DNMT3B. SPRY3 X- and Y-inactivation is associated with a differential enrichment of repressive histone modifications and the recruitment of Polycomb 2 group proteins compared to the active X allele. Another major factor in SPRY3 repression is late replication; the inactive X and Y alleles of SPRY3 have delayed replication relative to the active X allele, even in ICF syndrome cells where the closely linked SYBL1 gene is reactivated and advanced in replication. The relatively stable maintenance of SPRY3 silencing compared with SYBL1 suggests that genes without CpG islands may be less prone to reactivation than previously thought and that genes with CpG islands require promoter methylation as an additional layer of repression.
Received November 14, 2005
Revised January 20, 2006
Accepted February 10, 2006
Article
Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications
M. L. De Bonis 1,
A. Cerase 1,
M. R. Matarazzo 1,
M. Ferraro 1,
M. Strazzullo 1,
R. S. Hansen 2,
P. Chiurazzi 2,
G. Neri 2,
and
M. D'Esposito 3 *
2 Department of Genetics, University of Washington, Seattle, USA; Institute of Medical Genetics, Catholic University, Rome, Italy
3 Institute of Genetics and Biophysics ‘A. Buzzati Traverso’ CNR, Via P. Castellino, 111, 80131, Naples, Italy
M. D'Esposito, E-mail: desposit{at}igb.cnr.it
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. R. Matarazzo, S. Boyle, M. D'Esposito, and W. A. Bickmore Chromosome territory reorganization in a human disease with altered DNA methylation PNAS, October 16, 2007; 104(42): 16546 - 16551. [Abstract] [Full Text] [PDF]
|
|