EPIc GENETICS

Epigenetics is basically the study of chemical modifications to DNA, which do not alter the genetic code itself, but the molecules involved do act to silence or promote gene expression. There are many different mechanisms involved in this process, but today I'm going to take you through my top 2. The first is known as DNA methylation. This is simply the addition of a methyl group to a base of the DNA (cytosine is converted to 5-methylcytosine for example), and it is controlled by 3 different enzymes: DNA methyltransferase (DNMT) 1, DNMT 3A and DNMT3B. These enzymes are examples of epigenetic "writers" (thank you Nessa Carey for the great analogy), as they actually create the epigenetic code, by adding methyl groups to CpG motifs of genes, creating an epigenetic mark. Highly methylated areas of the genome are less transcribed than those areas with fewer methyl groups added. But DNA methylation does not occur randomly, because most CpG motifs are concentrated just 'upstream' from specific genes, in their promoter regions where transcription factors usually bind. These are called CpG islands, and in around 60% of protein coding genes the promoters lie within these islands. Methyl groups binding in the CpG islands inhibit transcription factors from binding in the gene promoter region, and therefore more methyl groups = less transcription.

The other epigenetic mechanism that I particularly like is the histone modification; acetylation. Histones are proteins which chromosomes are bound to, in order to package DNA into nucleosomes, and acetylation involves adding an acetyl group to a specific lysine amino acid on the N-terminal tail of a histone (lysine converted to acetyl-lysine). Again, the acetylation does not alter the underlying genetic sequence, however it does promote gene transcription. Usually the reaction is catalysed by histone acetyltransferase, and is important in regulating transcription factors and effector proteins in our genome. The problem with histone modifications is that there are so many different processes, with different effects on gene expression, that a complex histone code is created. Even geneticists find it difficult to get to grips with, so let's not go into that...