Abstract
Epigenetics can be defined as all the meiotically and mitotically
inherited changes in gene expression that are not encoded in the
DNA sequence itself. Epigenetic modifications of chromatin and DNA
have been recognized as important permissive and suppressive factors
in controlling the expressed genome via gene transcription. Two major
epigenetic mechanisms are the posttranslational modification of histone
proteins in chromatin and the methylation of DNA itself, which are
regulated by distinct, but coupled, pathways. It is clear that the
epigenetic state is a central regulator of cellular development and
activation. Emerging evidence suggests a key role for epigenetics
in human pathologies, including in inflammatory and neoplastic disorders.
The epigenome is influenced by environmental factors throughout life.
Nutritional factors can have profound effects on the expression of
specific genes by epigenetic modification, and these may be passed
on to subsequent generations with potentially detrimental effects.
Many cancers are associated with altered epigenetic profiles, leading
to altered expression of the genes involved in cell growth or differentiation.
Autoimmune and neoplastic diseases increase in frequency with increasing
age, with epigenetic dysregulation proposed as a potential explanation.
In support of this hypothesis, studies in monozygotic twins revealed
increasing epigenetic differences with age. Differences in methylation
status of CpG sites, monoallelic silencing, and other epigenetic
regulatory mechanisms have been observed in key inflammatory response
genes. The importance of the epigenome in the pathogenesis of common
human diseases is likely to be as significant as that of traditional
genetic mutations. With advances in technology, our understanding
of this area of biology is likely to increase rapidly in the near
future.
- aging,_genetics
- autoimmune_diseases,_genetics
- chromatin,_genetics
- disease
- dna_methylation
- environment
- epigenesis,_genetic,_genetics
- gene_expression_regulation,_genetics
- histones,_genetics
- humans
- inflammation,_genetics
- neoplasms,_genetics
- nutrigenomics
- transcription,_genetic,_genetics
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