What is Epigenetics?

What is epigenetics?

Have you ever wondered what determines the differences between cells in our body? What determines the differences between identical twins? How a butterfly develops from a caterpillar? Because all cells in our body have an identical DNA sequence (deoxyribonucleic acid - DNA). Identical twins have an identical genetic material. Caterpillar and butterfly have the same DNA sequence ...

Epigenetics is the study of potentially inheritable modifications of our genome (the DNA) that can determine these differences without altering the DNA sequence.

The Human Body - Diverse Cells, a DNA

DNA is our genetic material and contains the necessary information (in the form of genes) that cells need to perform their functions.

There are genes that every cell in our body needs. These include genes needed for cell division (mitosis) or DNA repair in the case of damage. On the other hand, there are genes that are needed for cell-specific functions, such as the electrochemical signaling of neurons in our brain, the cleaning function of the liver or the muscle function.

All of our cells develop during early stages of development of so-called 'stem cells'. Stem cells, as well as all adult cells in our body have the same DNA sequence and thus the same genes.

How are these differences determined?

The answer to this question lies in the packaging of DNA in the nucleus. Our DNA, when fully extended, is about 2 meters long. In order to fit in the 6 microns (1x10-6 meters) cell nucleus, it must therefore be compressed several times:

* First the DNA is twisted into a double helix (Watson and Crick, 1953 & Nobel Prize 1962).

* The next stage of packaging involves so-called histone proteins. These proteins form eight-part complexes (octamers), which consist of four different proteins (H2A, H2B, H3 and H4), which are present twice each. The twisting of DNA by histone octamers results in a regular DNA-protein 'chain'. A protein-DNA unit in this 'chain' is called the nucleosome (Kornberg, 1970). The whole 'chain' is called the chromatin.

* Finally, the chromatin is wound several times to fit into the cell nucleus.

Under the microscope one can see that different regions of the genome are packed in different densities in the cell nucleus. This is different in different cell types. Very densely packed regions are called 'heterochromatin' and open regions are called 'euchromatin'. Thereby, the accessibility of genes to cell machinery and thus the gene activity can be regulated. Genes that are not needed by cells are tightly packaged and turned off ('hidden'), and genes that require cells for their functions are less tightly packed ('open'). Thus, the packaging level may be a 'START' or 'STOP' sign for the cell to use certain genes and ignore others.

The degree of packaging of the DNA can be influenced in various ways. On the one hand by chemical modifications of the DNA and associated histone proteins and on the other hand by mechanical movement of the nucleosomes.

The study of these mechanisms is epigenetics.

'Epi' = above / on (ancient Greek)

'Epigenetics' = above / on genetics; Mechanisms of gene regulation that do not alter the underlying genetics / DNA sequence. Epigenetic changes, like the DNA sequence, are potentially inheritable.

The following sections discuss epigenetic mechanisms, their expression on humans and nature, and evidence of their heredity from modern research.

Summary

The DNA is packed in several stages in the cell nucleus.

Different regions of the genome are packed in different densities.

Differences in the packaging affect the accessibility of genes to factors (e.g., transcriptional machinery).

The DNA packaging can be influenced by chemical modifications of the DNA and histones as well as by mechanical displacement of the nucleosomes.

These modifications are called epigenetic modifications.