Carcinogenesis Advance Access published online on January 16, 2004
Carcinogenesis, doi:10.1093/carcin/bgh066
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CANCER BIOLOGY
1 Department of Medical Oncology, Cancer Research UK Beatson Laboratories, Glasgow University, Glasgow, G61 1BD, UK
* Corresponding author. E-mail: g.strathdee{at}beatson.gla.ac.uk.
Received 17 September 2003
; revised 5 December 2003
; accepted 16 December 2003
Over 50% of human genes are associated with CpG islands and DNA methylation within such CpG islands has been clearly correlated with inhibition of expression. Whereas changes in DNA methylation play a key role in a number of human diseases, in particular cancer, in normal DNA CpG islands are nearly always methylation free regardless of the expression status of the associated gene. Only limited evidence supports a role for DNA methylation in controlling tissue specific expression in adult somatic tissue. Loss of expression of the MCJ gene has previously been linked to increased chemotherapeutic drug resistance in ovarian cancer. We report that loss of expression of MCJ in drug resistant ovarian cancer cell lines depends on methylation of a CpG island within its first exon, but is independent of methylation within the promoter region. Furthermore, cell type specific expression of the MCJ gene in normal cells also depends on the methylation status of the CpG island within its first exon. The MCJ CpG island is methylated, and the gene is not expressed in cells of epithelial origin but unmethylated and expressed in cells of lymphocyte or fibroblast origin. Chromatin immunoprecipitation assays determined that MCJ CpG island methylation was associated with loss of histone acetylation in ovarian epithelial cells compared to unmethylated fibroblast cells. Reduced acetylation was observed not only within the CpG island, but also within the promoter region, suggesting that CpG island methylation may direct alterations in chromatin structure within the promoter region, leading to gene inactivation.
Cell type specific methylation of an intronic CPG-island controls expression of the MCJ gene
2 Department of Surgery, The Medical School, University of Newcastle, Newcastle-Upon - Tyne NE2 4HH, UK
3 Cancer Research UK Beatson Laboratories, Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK
4 Department of Gynaecological Oncology, Stobhill Hospital Glasgow G21 3UW, UK
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Longoni, F. Orzan, M. Stroppi, N. Boari, P. Mortini, and P. Riva Evaluation of 1p36 markers and clinical outcome in a skull base chordoma study Neuro-oncol, February 1, 2008; 10(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Hatle, W. Neveu, O. Dienz, S. Rymarchyk, R. Barrantes, S. Hale, N. Farley, K. M. Lounsbury, J. P. Bond, D. Taatjes, et al. Methylation-Controlled J Protein Promotes c-Jun Degradation To Prevent ABCB1 Transporter Expression Mol. Cell. Biol., April 15, 2007; 27(8): 2952 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Strathdee, A. Sim, R. Soutar, T. L. Holyoake, and R. Brown HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia Carcinogenesis, February 1, 2007; 28(2): 299 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K M Davey, J S Parboosingh, D R McLeod, A Chan, R Casey, P Ferreira, F F Snyder, P J Bridge, and F P Bernier Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition J. Med. Genet., May 1, 2006; 43(5): 385 - 393. [Abstract] [Full Text] [PDF]
|
|