Skip Navigation



Nucleic Acids Research Advance Access published online on November 22, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm1028
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (4033K) Freely available
Right arrow Screen PDF (754K) Freely available
Right arrowOA All Versions of this Article:
36/1/330    most recent
gkm1028v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Li, D.
Right arrow Articles by Zhao, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, D.
Right arrow Articles by Zhao, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

CpG methylation plays a vital role in determining tissue- and cell-specific expression of the human cell-death-inducing DFF45-like effector A gene through the regulation of Sp1/Sp3 binding

Dong Li, Liang Da, Hong Tang, Tsaiping Li and Mujun Zhao*

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

*To whom correspondence should be addressed. Tel: +86-21-54921115; Fax: +86-21-54921011; Email: mjzhao{at}sibs.ac.cn

Received August 2, 2007. Revised October 26, 2007. Accepted October 29, 2007.

Cell-death-inducing DFF45-like effector A (CIDE-A) belongs to a family of proapoptotic proteins, the expression of which is highly restricted in human tissues and cells. Here, the core region of the human CIDE-A promoter was characterized. Surprisingly, two Sp1/Sp3-binding sites, rather than tissue-specific transcription factors, were found to be required for the promoter activity. Although the ubiquitously expressed Sp1 and Sp3 were crucial, they alone could not adequately regulate the specific expression of CIDE-A. We found that the expression of CIDE-A was further regulated by CpG methylation of the promoter region. By performing bisulfite sequencing, we observed dense CpG methylation of the promoter region in tissues and cells with low or no expression of CIDE-A but not in tissues with high level of CIDE-A expression. In vitro methylation of this region showed significantly reduced transcriptional activity. Treatment of CIDE-A-negative cells with 5-aza-2'-deoxycytidine demethylated the CpG sites; this opened the closed chromatin conformation and markedly enhanced the binding affinity of Sp1/Sp3 to the promoter in vivo, thereby restoring CIDE-A expression. These data indicated that CpG methylation plays a crucial role in establishing and maintaining tissue- and cell-specific transcription of the CIDE-A gene through the regulation of Sp1/Sp3 binding.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.