Wednesday, 4 April 2012

Epigenetics in Developmental Genes

Epigenetics in Developmental Genes

Intuitively, if gene expression is considered, it is easily realised that there is more at work than just DNA.  New perspectives have been created with the advancement in epigenetics. 
Epigenetics can basically be summed up as the study of changes in heritable gene expression, without alterations in the DNA sequence.  The causes of these changes have been found to be non-genetic mechanisms such as DNA methylation, histone modifications, chromatin condensation and small RNA’s. 

Epigenetics are able to regulate gene expression and are not surprisingly quite central to development and cellular differentiation (specialised function).  An interesting yet crucial side note, is that epigenetic modifications are actually reversible even if that modification has been apparent through several generations.  The reversibility is due to the fact that the modification appeared in the first place in response to an environmental cue.  An interesting group of genes which have been placed under extensive study are Hox genes.  The importance of these genes are deeply rooted in the fact that under epigenetic regulation, they are responsible for embryo development and stem cell differentiation. 

A characteristic of Hox genes are that they have collinear expression.  This means that within a Hox cluster, genes which are located in a more 3’ region will be activated earlier and in front of genes which are located in a more 5’ region.  This expression can be attributed to the epigenetic mechanism of a unidirectional chromatin opening from 3’ to 5’.  If this expression of Hox genes is disturbed, the order of development will be altered often leaving development incomplete.  An example of this can be seen in embryonic development, where if the expression of Hoxa3 gene is disturbed, the cells of the neural crest will not differentiate sufficiently and, thus the thymus is unable to form. So it can be clearly seen, how central epigenetic mechanisms are to the normal development and differentiation of cells.

The finding in epigenetics which has the most potential in a medical realm is that even if environmental cues are absent, the epigenetic mechanisms continue.  So it is quite obvious that an isolated cell contains epigenetic memory, which in turn allows genes such as Hox genes to create identical stem cells in vitro. 

It is clear how the cellular identity is, in fact, controlled by the epigenetic mechanisms, especially considering that the DNA sequence is the same for every cell. Future applications with increased study in the area of epigenetics in developmental genes, such as Hox genes, are immense.   Gene expressions have a particular profile or pattern (as epigenetics are heritable) which provides the cell with a positional identity, which is a necessary epigenetic cue for the differentiation of the cell.  For this reason when stem cells are produced in vitro, the characteristics of the lineage will be present.  In order to successfully accommodate stem cell transplants to host tissues, the gene profiles must be matched.  Research has already commenced for finding the answer to profile matching, and currently lies in trying to mimic the positional cues needed for the correct epigenetic responses to occur. This would allow for the production of cells which could replace any damaged or absent tissues in a host.

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