## How do epigenetic changes work?

Three main types of mechanisms are involved in the regulation of gene expression depending on epigenetic changes. The first of them is DNA methylation, which, among other things, is also responsible for switching off genes important for the development of the queen bee. It involves adding a small chemical tag – a methyl group – to DNA. Methylation of the fifth carbon of cytosine occurs most often, resulting in the modified base 5-methylcytosine. In eukaryotes, cytosines are almost exclusively methylated, which are adjacent to guanines and are connected to them by a phosphate group. Such a pair of nucleotides is called a CpG dinucleotide. Most CpG dinucleotides are found in gene promoters and help their expression by maintaining an open chromatin structure, which in turn allows access to the appropriate transcription factors that trigger the transcription of the gene in that region. However, the presence of methyl groups prevents regulatory proteins and transcription factors from accessing the DNA sequences necessary for the gene to be expressed. DNA methylation is a reversible process, as the methyl groups can be removed, a process of demethylation, and the gene is turned back on (Figure 6.6). Specific enzymes are responsible for the process of binding and removing the methyl group, while in most cases DNA methylation turns genes off and demethylation turns them on.

Histones are proteins whose task is to package DNA in the nucleus by wrapping it around itself. Such a structure of histones wrapped around DNA is called a nucleosome. Histones themselves can also undergo chemical modifications, if methyl groups are additionally attached to the histones, the nucleosomes are more tightly packed next to each other and prevent other proteins and enzymes from accessing the DNA. DNA packed in this way is called condensed chromatin - heterochromatin. Another chemical modification of histones is acetylation, which generally has the exact opposite effect. When an acetyl group is attached to histones, DNA is more accessible and genes can be expressed. Then we talk about relaxed chromatin - euchromatin (Figure 6.7). However, there are also places and situations where the effect of modifications on histones is opposite and acetylation turns genes off and methylation has the ability to turn on their expression. The changes in histone modification is more dynamic than DNA methylation, which is why heterochromatin can change to euchromatin and vice versa more often during the life of a cell.