The current state of "epigenetic" research in humans: promise and reality

John M Greally, Amanda Drake

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Conrad Waddington introduced the term epigenetics as the ‘branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being’. Over recent years epigenetic processes have been defined in many ways, from ‘a change in the state of expression of a gene that does not involve a mutation, but that is nevertheless inherited in the absence of the signal (or event) that initiated the change’ 1 to a much broader definition: ‘the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states’ 2. The lack of a clear, agreed definition means the term ‘epigenetic’ is now used to describe many processes associated with the control of gene expression, including DNA methylation, histone modifications and non-coding RNA (ncRNA), despite the fact that we do not know of biochemical mechanisms allowing histone modifications or ncRNA to be ‘heritable’ from parent to daughter cell through mitosis or meiosis. Here we focus on the most widely studied ‘epigenetic’ modification, DNA methylation, which occurs predominantly at cytosines in a CpG dinucleotide context.

In differentiated cells, DNA methylation patterns associate with gene silencing or activation. While there is ongoing debate over the extent to which changes in DNA methylation drive changes in transcription rather than reflect transcriptional changes or the actions of transcription factors 3, epigenetic marks do play an important role in mammals, including the establishment and maintenance of genomic imprinting, X-chromosome silencing and repetitive element repression. Diseases associated with mechanisms involving DNA methylation include Rett syndrome and disorders affecting the regulation/dosage/DNA sequence of imprinted genes e.g. transient neonatal diabetes, pseudohypoparathyroidism and syndromes such as Silver-Russell, Beckwith Wiedemann, Angelman, and Prader-Willi 4.
Original languageEnglish
Pages (from-to)103-104
JournalJAMA pediatrics
Issue number2
Early online date5 Dec 2016
Publication statusPublished - Feb 2017


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