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Myocardial molecular biology: an introduction
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  1. Nigel J Brand,
  2. Paul J R Barton
  1. Correspondence to:
    Dr Nigel J Brand, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science Technology and Medicine, Dovehouse Street, London, SW3 6LY, UK;
    n.brand{at}ic.ac.uk

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The recent publication of draft copies of the human genome sequence from both public and private sector consortia has fuelled anticipation that eventually, once all genes have been identified, we will be able to ascertain which of them are involved in human diseases, including those affecting the cardiovascular system. Understanding the molecular biology behind both inherited and acquired disorders is now viewed as essential to provide a full picture of the aetiology and progression of disease. Within the past decade considerable advances have been made in identifying the genetic basis of myocardial disorders such as familial hypertrophic cardiomyopathy and dilated cardiomyopathy, as well as the molecular signalling pathways and gene regulatory events that characterise acquired disease such as pressure overload induced cardiac hypertrophy. Furthermore, by defining the molecular processes underlying normal development we may be able to manipulate immature cell phenotypes such as those of embryonic stem cells or skeletal myoblasts to replace damaged, terminally differentiated cells such as cardiac myocytes. In this review we outline the basic principals of gene expression, the different mechanisms by which expression is regulated and how these can be examined experimentally.

DNA MAKES RNA MAKES PROTEIN

The blueprint for any organism is contained within its genome in the form of chromosomes and is written in the universal four “base” language of adenine (A), guanine (G), cytosine (C), and thymine (T). Chromosomes are built of chromatin, double stranded DNA wrapped around a multi-protein complex core comprised of histone proteins. This DNA contains the language (DNA or nucleotide sequence) that can be read and translated into proteins, and these areas of DNA are called genes.1, 2 In higher organisms, ranging from yeast to plants and man, practically all genes are interrupted, with sequences coding for protein (coding exons) separated by regions of non-coding DNA called introns. The …

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