Thanks to the Human Genome Project we now have a complete genomic map. But, simply having a map doesn’t give you all the information. For a map to be useful, you still need know where to go, the best way to get there and usually, how long it will take.
The genome project identified all the genes (about 25,000) that are needed to make a human. Every single one of those genes is contained within every cell. What the project didn’t tell us is how those genes get switched on and off to produce unique organs, individuals and diseases. So, in many ways, the map it provided raised as many questions as it answered.
This is where the epigenome.
To continue the metaphor of the genome as a map, the epigenome is the additional information that makes the map useful – the traffic lights, lane markings, public transport timetables and venue opening hours.
The epigenome is made up of several different types of chemical modifications. These are grouped as – [DNA methylation](http://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070](http://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070), histone modification and chromatin remodeling, and non-coding RNA.
DNA methylation is essentially the addition of common organic compounds (methyl groups) to DNA, which blocks genes from being read. This alters gene expression without changing the underlying genes themselves. Histones are the proteins that make up chromatin, the spool around which the DNA is wound. Chemical modifications can alter the structure of these proteins, changing the way the genes are exposed and unwound to be expressed.
RNA (ribonucleic acids) are similar in structure to DNA. Normally, when genes are expressed, DNA is copied into RNA and then into proteins. Non-coding RNAs are special RNAs that have other biological functions, such as binding to other RNA to stop them from becoming proteins.
Importantly, while the genome is fixed, the epigenome is fluid and dynamic; changing in different tissues, at different stages in development and in response to environmental exposures and lifestyle habits. It can be modified by what we eat and drink, smoking, ageing, stress, pollution, sun exposure and countless other environmental factors.
Understanding the epigenome in “normal” tissue will help us to identify how and when changes and “mistakes” in the epigenome lead to disease. Its role in conditions, such as heart disease, asthma, autism and cancers are all being investigated.
Since the Human Genome Project was completed in 2003, several projects have been trying to do for the epigenome what it did for the genome. This is more complex because each organism will have several epigenomes, depending on tissue type, age and environmental influences, among other things. This means that the epigenome requires multiple maps to be created in multiple samples, from multiple tissues, cells and situations.
The most comprehensive of these projects is the Roadmap Epigenomics Project. Launched in 2008, the consortium behind this project aims to produce a publicly accessible epigenomic map of “normal” cell and tissues, by mapping all the epigenomic features in hundreds of cell populations (cell lines, stem cells and primary tissues).
This work will be complemented by other major epigenomic initiatives, such as the International Human epigenome consortium (set up to accelerate and coordinate epigenomics research worldwide), The Human Epigenome Project (mapping methylation variable positions across the genome) and ENCODE (aims to catalogue all the functional elements in the human genome, including epigenomics).
A map of the epigenome will explain how environmental exposures and lifestyle habits lead to disease. By understanding normal patterns of the epigenome, we can pinpoint the mistakes or changes in the epigenome that cause diseases from cancer to mental illness. And it will offer new and exciting targets for drugs to treat diseases that have epigenetic components.
The voyage into this new frontier shows that while the Human Genome Project gave us unprecedented amounts of information about our existence, it was only the first step in explaining how and why we are what we are.