Skip Navigation



Carcinogenesis Advance Access published online on July 21, 2006
Carcinogenesis, doi:10.1093/carcin/bgl133
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary data
Right arrow All Versions of this Article:
28/2/299    most recent
bgl133v1
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 arrowRequest Permissions
Google Scholar
Right arrow Articles by Strathdee, G.
Right arrow Articles by Brown, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Strathdee, G.
Right arrow Articles by Brown, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received January 24, 2006
Revised July 5, 2006
Accepted July 12, 2006

CANCER BIOLOGY

HOXA5 is targeted by cell type specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia

Gordon Strathdee 1 *, Alyson Sim 1, Richard Soutar 2, Tessa L. Holyoake 3, and Robert Brown 1

1 Centre for Oncology & Applied Pharmacology, CR-UK Beatson Laboratories G61 1BD, UK
2 Department of Haematology, Western Infirmary, Dumbarton Road, Glasgow, G11 6NT UK
3 Division of Cancer Sciences & Molecular Pathology, University of Glasgow, Glasgow, G31 2ER, UK

* To whom correspondence should be addressed.
Gordon Strathdee, E-mail: g.strathdee{at}beatson.gla.ac.uk


  Abstract

HOXA5 is a member of the HOX gene family, which are known to play key roles during embryonic development and in differentiation of adult cells. In addition, HOXA5 has been implicated as a tumour suppressor in breast cancer and shown to transactivate the p53 gene. CpG island methylation is a common mechanism of gene inactivation in tumour cells, but is rarely involved in control of cell type specific expression in normal cells. However, here we demonstrate that HOXA5 is one of the small number of genes whose cell type specific expression pattern is controlled by cell type specific CpG island methylation in normal cells. Furthermore, chromatin immunoprecipitation analysis identified novel patterns of histone modifications associated with DNA methylation of HOXA5. High levels of methylation of histone residues (lysine 9 and 36 of histone H3) previously associated with transcriptional repression were present in the unmethylated, actively transcribing state, and were then reduced following DNA methylation and gene inactivation. Alterations to the normal patterns of HOXA5 gene methylation were also observed in tumour cells. Quantitative analysis of HOXA5 methylation identified the presence of limited methylation in all of the breast, lung and ovarian tumours examined. However, methylation levels in these three tumour types were nearly always low and comparable to that detected in the corresponding normal tissue. In contrast, acute myeloid leukaemia (AML) samples frequently (60% of samples) exhibited very high methylation levels, far greater than that seen in normal haematopoietic cells, suggesting a role for hypermethylation of HOXA5 in the development of AML, consistent with its previously identified role in haematopoietic differentiation.

Keywords: HOXA5; DNA methylation; chromatin; cell type specific; AML.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
G. Strathdee, T. L. Holyoake, A. Sim, A. Parker, D. G. Oscier, J. V. Melo, S. Meyer, T. Eden, A. M. Dickinson, J. C. Mountford, et al.
Inactivation of HOXA Genes by Hypermethylation in Myeloid and Lymphoid Malignancy is Frequent and Associated with Poor Prognosis
Clin. Cancer Res., September 1, 2007; 13(17): 5048 - 5055.
[Abstract] [Full Text] [PDF]


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.