Skip Navigation

Cardiovascular Research 1998 38(3):736-743; doi:10.1016/S0008-6363(98)00058-3
© 1998 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Clifford, C.P.
Right arrow Articles by Nunez, D.J.R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clifford, C.P.
Right arrow Articles by Nunez, D.J.R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1998, European Society of Cardiology

Human β-myosin heavy chain mRNA prevalence is inversely related to the degree of methylation of regulatory elements

C.P. Clifford and D.J.R. Nunez*

Section on Clinical Pharmacology, Division of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK

* Corresponding author. Tel.: +44 (181) 383 3219; Fax: +44 (181) 383 2066; E-mail: d.nunez@rpms.ac.uk

Objective: Methylation of cytosine in CG dinucleotides within regulatory elements is believed to silence gene expression. These dinucleotides occur in certain important regulatory elements in the promoter region of the human β-myosin heavy chain (β-MHC) gene. We therefore investigated whether methylation of these elements correlates with β-MHC gene transcription in human ‘expressing’ (right atrial) and ‘non-expressing' (peripheral blood leucocytes) cells. Methods: We employed 2 techniques to assess promoter methylation: (i) analysis of the susceptibility to digestion of a particular CCGG restriction site in the promoter region when genomic DNA is cleaved with the restriction endonucleases MspI (methylation-insensitive) and HpaII (methylation-sensitive), and (ii) the bisulphite-PCR method to examine in detail the methylation patterns of 3 important regulatory elements that contain CG dinucleotides. β-MHC mRNA expression in right atrium and leucocytes was assessed using reverse-transcription-PCR with specific primers that do not detect {alpha}-MHC cDNA. Results: The digestion pattern observed with MspI or HpaII indicated that the CCGG site was almost completely methylated in leucocytes, but relatively unmethylated in atrial myocardium from the same patients. When methylation was examined with the bisulphite-PCR method we found a reciprocal relationship between the level of β-MHC mRNA expression in leucocytes and atrial myocardium and the degree of methylation of CG dinucleotides in the 5' regulatory elements of the gene. Conclusions: Tissue-specific methylation of the human β-MHC gene promoter may play a role in determining the pattern of expression of this gene. Furthermore, alteration of the level of methylation may underlie the changes in transcription of this gene that occur, for example, when atrial or ventricular myocardium hypertrophies.

KEYWORDS Human; Myosin; DNA methylation; Hypertrophic cardiomyopathy; Bisulphite; Gene expression; Heart; RT-PCR


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
 J. Nutr.Home page
G. L. Johanning, D. C. Heimburger, and C. J. Piyathilake
DNA Methylation and Diet in Cancer ,
J. Nutr., December 1, 2002; 132(12): 3814S - 3818.
[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.