I know this review is almost a year old but is very important.
The science of Epigenetics was in part developed by Waddington and his influence flows through these articles.
This is an important area for nutrition and is a rich source of ideas and research projects.
Epigenetics is the study of heritable changes in gene expression that are not due to changes in DNA sequence. Epigenetic changes allow for the differentiation of various cell types in an organism and cellular processes. X-chromosome inactivation in the female mammal is an example. This control may be upset by the aging process, neoplastic transformation, chronic inflammation and exposure to noxious influences and even by nutrition though this an unexplored area.
Epigenetic change may be de to chemical changes in the DNA or histones and also there is a role for RNA in this mechanism.
There are two well known epigenetic systems the Polycomb and Trithorax and DNA methylation.
The Polycomb and Trithorax are a group of proteins which maintain repressed or active transcription states of developmentally important genes. This system has a memory which can be transmitted to the next generations.
DNA methylation is associated with stable gene silencing eg the inactivation of the second X chromosome in the female mammal.
There are additional complex changes in protein complexes which regulate transcription. Changes in chromatin packing and histone modification the protein that packs around the DNA modify transcription.
A further modifying influence on gene activity is its position in the three dimensional structure of the chromosome, that is the manner in which the chromosome is shaped and the position of the chromosome in the nuclear structure and whether the gene is available for biochemical activity or hidden. This may vary from cell to cell and the activity of that cell and determine the cell’s function.
During development, cells are in a genetic state, from which they can differentiate into many cell types, and progressively become differentiated. . Their gene-expression programmes become more defined, restricted and fixed. . Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, with short-term, and flexible, epigenetic silencing. The methylation of DN A gives long-term epigenetic silencing of particular sequences — transposons, imprinted genes and pluripotency-associated genes in somatic cells. Long-term silencing can be reprogrammed by demethylation of DN A, and this process might involve DNA repair.
When there is change in these processes then disease may occur. The interesting situation is in repair and response to injury and inflammation and possibly malnutrition.
Nature Insight editor Campbell,2007 Epigenetics Nature vol 447, pp395-440
- Martin Eastwood