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The sequence of the human genome marked not the end of the genomics field but it’s beginning. After almost a decade that the first human genome was sequenced and published researchers have a long way ahead to understand the meaning of all this information. This is mainly because there is another level of information beyond the genome that is the epigenome. For example, if the genome is the aphabet, the epigenome is the way the words are typed - in bold, italic - giving emphasis to the text. The epigenome is defined as the group of modifications that can occur in our genomes that will not change the sequence of the bases in the DNA but can change the DNA conformation and as a consequence change the expression of genes. Epigenetics is the study of the modifications in the DNA or the epigenome. These modifications that occur in the DNA molecule can be divided in three: (1) binding of different proteins to the DNA such as histones; (2) addition of chemical groups in the bases of the DNA such as methyl (CH3) groups and (3) microRNAs and other non-coding RNAs that can regulate the expression of genes.
Main components of epigenomics:
Histone protein positioning in the DNA and their modifications can influence the binding of regulatory proteins to the chromosomes turning genes on or off; DNA methylation in the cytosines of the DNA molecule is associated to gene silencing and closed chromatin inactivating several genes in a coordinated manner; and non-coding RNAs such as microRNAs can regulate genes and influence gene silencing in our genome by mechanisms such as degradation of the message produced by the genome.
Implications of epigenetics and epigenomics to diseases:
Epigenetic changes in cells are implicated in a variety of different diseases. This is mainly because epigenetic mechanisms are the basis for development. Different types of cancer have been associated to defects in epigenetic mechanisms such as DNA methylation and modifications of the histones. Several neurological disorders are also associated to epigenetics such as Angelman Syndrome, Prader-Willi Syndrome, etc. For example, fascinating disorders involving chromatin-modifying genes and epigenetics is the ICF syndrome, which stands for immunodeficiency, chromosome instability, and facial anomalies and Rett Syndrome that is caused by mutations in an enzyme named Methyl binding protein 2 (MECP2) that can bind to methyl groups in the DNA.
Drugs being developed based on epigenetics:
Decitabine: this drug acts by inhibiting one enzyme that can regulate DNA methylation. Since several cancers have important genes turned off by DNA methylation, inhibition of the enzyme that regulates this mechanism is able to turn these genes on and change the cell phenotype to a “normal” state. This drug was already approved by the FDA for some types of cancer.
Zolinza or Vorinostat: this drug inhibits the binding of enzymes named histones to the DNA and changing the gene expression pattern of a cell. By inhibiting these enzymes, genes are re-expressed and the cells can change their phenotype. This drug was also approved for some types of cancer.
The Human Epigenome Project (HEP) aims to identify, catalogue and interpret genome-wide DNA methylation patterns of all human genes in all major tissues. DNA methylation is the only flexible genomic parameter that can change genome function under exogenous influence. Hence it constitutes the main and so far missing link between genetics, disease and the environment that is widely thought to play a decisive role in the etiology of virtually all human pathologies.
Companies in the epigenetics field:
Exact Sciences is a molecular diagnostics company focused on colorectal cancer. The company offers non-invasive, molecular screening technologies for the detection of colorectal cancer using a combination of DNA methylation markers. Stool-based DNA (sDNA) technology is included in colorectal cancer screening test s provided by Exact Sciences. The American Cancer Society and the U.S. Multi-Society Task Force on Colorectal Cancer has already included it in their guidelines.
Epigenomics AG develops diagnostic tests that detect differences in DNA methylation pattern between healthy and sick individuals or between subgroups of patients for disease classification. This company is the leader in DNA methylation technologies and biomarkers.
OncoMethylome Sciences develops DNA gene methylation tests to assist physicians (i) in detecting cancer at an early stage with a high level of accuracy and (ii) in predicting a patient’s response to cancer therapy or the likelihood of cancer recurrence.
Sequenom is committed to providing the best genetic and epigenetic analysis products that translate genomic science into superior solutions for biomedical research, agricultural applications, molecular medicine and non-invasive prenatal diagnostics research, and potentially, clinical utility.
Invitrogen offers solutions, products and services that enable a deeper understanding of the nature of gene regulation with a special focus in epigenetics.
For more information on epigenetics and epigenomics see:
Costa FF. Non-coding RNAs, epigenetics and complexity. Gene. 410(1):9-17, 2008.
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