Hi all,
I thought i would write a little piece about Epigenetics. I am working in a lab in the UK and this is the sort of stuff i work on.
Epigenetics is classically defined as inheretence without alteration to the DNA sequence. Essentially though it is inheretence at the cellular level, not organisms. So when a stem cell asymetrically divides, it will produce two daughter cells, another stem cell and a blood cell for example. Epigenetics determines how these two different cell trypes, with identical DNA, can be derived. The epigenetic processes at work switch of some developmentally required genes, and switch on others, thus transforming the fate, function and behaviour of the cell. For those of you out there with some biological degree, this is essentially what Lamark described in his view of evolution (the competing theory to Darwin in the late 1800's). It appears he wasn't so far off the mark after all. Now though the term has been broadened to include regulation of gene expression but does not neccessarily require the daughter cells to 'remember' these changes.
There is a huge amount of DNA in each individual cell, about 2 meters if it were laid out in a line. However it is very thin so is able to be packaged into the nucleus of the cell, and is done so in a highly organised and efficient way through an interaction with Chromatin. Chromatin is essentially the name given to the protein case which wraps around DNA. DNA is wrapped around specific protein complexes called nucleosomes (146bp of DNA around 1 nucleosome and about 54bp of 'linker DNA between nucleoomes). The nuceosome complexes (made of 8 histone proteins) have 'loose and waving about' tails. They determine how tightly the DNA is coiled up, whether other proteins can see the DNA and physically interact with it, they determine if a gene can be expressed (like the haemaglobin gene in a red blood cell) and turned into protein or if it will be permanently silenced (as in the case of a blood cell gene in a neuron) or transiently silened as in the case of most genes in stem cells.
The histone tails confer these characteristics through what are called 'post-translational modifications' (PTMs), this is a term we give to changes (covalent) made to a protein after it has been translated from the RNA intermediary between DNA and protein. (DNA is traanscribed to RNA which is in turn translated to protein). The PTMs confer huge amounts of extra information to the protein, such as its activity level, its interaction partners and even the affinity it has for DNA. So when histone tails become methylated (a form of PTM) their affinity for DNA increases, thus winding up the DNA into tighter and tighter coils so it can not be accessed by the molecular machinery which allows genes to be expressed through the process of transcription (writing DNA into RNA, before the RNA is tranlasted to protein). On the flip side to this is acetylation (another form of PTM). Acetylation actually reduces the binding between DNA and the histones thus relaxing the DNA chromatin structure and exposing the DNA to the nuclear meliue where it can be access by the transcription machinery.
The balance between methylation and acetylation are at the heart of modern Epigenetics, their levels are determined by many factors, but other genes, your food and exercise levels as well as disease play the leading roles.
If any of you want to find out more then Wikipedia is a good place, you can search for terms like TriThorax and PolyComb, Histone and nucleosome, DNA compaction, enhancers, promoters and transcription start sites and transcription factors.
Also, if you want any more from me then let me know an i can try to give a few specific examples. I will try to post some more on epigenetics and how it relates to some elements in Siglers novels, there is probably quite a bit.
James
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