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Epigenetics refers to the covalent modifications found in
chromatin, on both the DNA and the accompanying histone proteins.
The narrowest definition would encompass only those modifications
that can be transmitted down cellular generations, but the
term is more commonly used to describe all such alterations,
whether these are heritable or transient. Indeed, much of
the current research focus in the field is on the relatively
transient changes because of the importance of these changes
in influencing gene expression and hence cellular activity.
A wide range of epigenetic modifications (or “marks”)
have been identified. Methylation is the commonest change
in DNA, but a much greater range of modifications has been
found on histone proteins including methylation, acetylation,
phosphorylation, neddylation, SUMOlation and ubiquitinylation.
The establishment or removal of these marks is a complex and
dynamic process, and is also processive as the presence or
absence of a particular modification on a histone protein
influences the other modifications that can be achieved.
The control of epigenetic modifications and their downstream
effects on gene expression operates at all levels of the cellular
machinery. Stimuli are converted into signalling pathways
leading to the nucleus, where they influence the enzymes that
modify chromatin. Differentially modified chromatin binds
different complexes of proteins which affect gene transcription.
Multiple epigenetic affectors and effectors will be present
and active in a cell at any given moment, operating in complex
and interacting networks. These networks may be further modulated
by the actions of non-coding RNAs including microRNAs.
Members of CellCentric’s network of scientists are
investigating all levels of the epigenetic pathways, from
a variety of technological and biological angles, leading
to new opportunities in drug discovery.
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