The Roles of Epigenetics in Heredity and Normal Functioning

he genetic code of each and every individual organism can tell a lot about its ancestors, some basic characteristics, and biases toward potential diseases. However, there are differences between individuals and species that are not recorded in the 4-letter genetic code but its packaging and handling. Epigenetics is defined as any factor influencing gene expression. Epigenetic mechanisms are important for normal function while their malfunction may lead to several diseases including cancer. They also take place in heredity and might be used to endow acquired traits.

Epigenetic Mechanisms

The DNA an organism carries encodes for all the proteins needed in any tissue at any time (and some nonprotein coding genes). The expression of each gene should be tightly regulated in time and space in order for a specific cell and the entire organism to function. Mutations in the genes or the factors controlling their regulation might lead to malfunctioning. For an instance, Prader-Willi syndrome is caused by genetic and epigenetic errors to the same part of chromosome 15. Every internal factor determining the gene expression profile can be considered as an epigenetic mechanism, two of which, DNA methylation and histone modifications, are the major ones.

DNA methylation is a modification in which a small molecule is attached to the DNA bases, usually Cytosine ones. DNA methylation occurs in all vertebrates, as far as scientists know. The modification silences the expression of the genes near the modification site leading to differential gene expression.

Another mechanism utilizes the histones to exert its function. The DNA should be tightly packed to fit into the nucleus. A set of proteins called histones does the packaging. These proteins wrap DNA around them and interlink to stabilize the packaging. The histones can be modified by the addition of an acetyl or methyl group to their tails. Different modifications lead to different levels of DNA accessibility around the histones and its overall expression levels. Histones modifications are sometimes used to force a specific gene expression profile in a certain tissue or at a certain time.

DNA Methylation and Heredity

DNA methylation is pre-set but can be changed during life hence adaptation to the environment can be achieved using this mechanism. The methylation pattern is changed throughout life but these changes are not transferred to the offspring. During embryogenesis, there are proteins that delete all the acquired methylation and remethylate the DNA in predefined positions. In some cases, however, the parental methylation is kept, allowing the heredity of acquired traits. Endowing acquired phenotypes using methylation supports Lamarck’s evolution theory.

Epigenetic mechanisms from gene to proteinOne example of such a process was observed in inheritance of coat color in mice (‘Epigenetic inheritance at the agouti locus in the mouse’ by Hugh D. Morgan et al. published in 1999(23) issue of Nature genetics) where mothers carrying the same genetic code had varying coat colors and endowed this phenotype to their young. It was observed that DNA methylation pattern of a specific locus differentiated between mice with different coat colors and as a conclusion DNA methylation was thought to take part in this epigenetic inheritance.

However, in a later report (‘Dynamic Reprogramming of DNA Methylation at an pigenetically Sensitive Allele in Mice’ by Marnie Blewitt et al., April 2006, PLoS Genetics) it was found that the methylation in the differentially methylated DNA is cleared during embryogenesis and the DNA is being remethylated, later on, suggesting that, at least in this case, epigenetic inheritance is not mediated by DNA methylation.

Epigenetics and Cancer

Although cancer is considered to be a genetic disease, some tumors have a normal genetic code but a disturbed epigenetic one. Research headed by Jorg Ellinger and published in September 2009 in the journal The Prostate entitled ‘Global levels of histone modifications predict prostate cancer recurrence’ finds that prostate cancer cells have much less modified histones compared to normal cells.

Occasional, unwanted epigenetic changes can cause cancer. Research published on August 2008 in the Mammalian Genome journal by Nicola Valeri et al. entitled ‘Epigenetics, miRNAs, and human cancer: a new chapter in human gene regulation’, introduces a mechanism for tumorigenesis based on epigenetic changes alone. The described model involves miRNA. Altering the modifications on the histones can generate cancer or participate in the overall cancerous effect.

DNA carries the code shaping an organism and an individual, but this code is not complete without the epigenetic one. Modifications related to DNA expression and packaging can alter the organism’s phenotype, taking a crucial role in the evolutionary process. The epigenetic code can be changed and endowed to the offspring, in oppose to the stable genetic one. Epigenetic inheritance can enable the heredity of acquired phenotypes. This kind of inheritance could be considered as a modern version of Lamarck’s Idea.