When we think about biological traits, we often associate them with genetics, mostly referring to the gene sequences within our genomes. The building material of our genome, the DNA, is composed of four nucleobases and a sugar backbone. The four bases make up what we call the genetic code. Three such bases in a row, called a codon, encode one of twenty amino acids. 4 out of the 64 possible codons signal the start or end of a protein coding sequence. But genetics is not all the information there is that influences our personal traits. There is literally another “layer” of information on top of the genetic code: Epigenetics. The Greek work “epi” meaning “on” refers to the chemical changes of the DNA or surrounding proteins that affect how the body can read genes. While genetics determine a protein’s sequence, epigenetics can change what proteins are synthesized, where, and at what time. As opposed to mutations within DNA sequences, epigenetic changes are reversible. Epigenetics are heritable but show dynamic plasticity in response to environmental cues. The changes are essential to normal and adaptive differentiation and development of organisms.
The human genome is quite large in size. Rolled out, the genome of a single cell would make a string almost two meters long. This vast length is stored tightly packed around proteins called histones in complexes referred to as nucleosomes. DNA that is packed in nucleosomes is inaccessible to the cellular machinery producing messenger RNA which ultimately prevents protein synthesis. Adding or removing chemical groups from amino acids such as lysine in histones can change the state of packing and thus the accessibility. Such patterns of access and tight packing are called chromatin architecture and can determine basically anything happening within a cell.
DNA modifications such as the addition of methyl groups to the nucleobases alter if, when, where or how much an accessible gene is transcribed into messenger RNA. They also play a role in genomic imprinting and the inactivation of one of the female X chromosomes to accommodate the imbalance between XX and XY. A descriptive example of X inactivation is the fur color of calico cats which are almost all females. Fur pigmentation in cats is linked to the X chromosome. Each cell randomly inactivates one X leading to orange or black fur.
The enzymes involved in epigenetics can be readers, writers and erasers of modifications. Enzymes introducing the chemical modifications on histones and DNA are writers. Enzymes proficient in identifying and interpreting the modifications are called readers. Enzymes dedicated to removing the modifications are referred to as erasers. Together they regulate an intricate pattern of chromatin architecture and gene expression.
Another important factor in epigenetics is non-coding RNA. Non-coding RNAs have amongst many functions been shown to recruit DNA epigenetic writers. More about non-coding RNA can be found in another article.
While some epigenetic changes are inherited, cells change their behavior and development in response to the environment. A cell is exposed to a plethora of signals from its environment and can adjust its activity to the circumstances via elaborate signaling cascades involving the epigenetic enzymes. Epigenetics change according to how much we exercise, how stressed we are, what we eat and where we live. Smoking will affect your genes as well as your epigenetics. Epigenetic changes have also been implicated in several diseases such as cancer. The modifications can inactivate tumor suppressors or alter a cells capability to repair DNA damage. Certain epigenetic markers can be used as means for early cancer detection and the writers, readers and erasers are promising targets for cancer therapies that aim to correct aberrant epigenetics.
