Epigenetics can be defined as a change in phenotype that is heritable but does not involve a change in the nucleotide sequence in DNA; that is, a change in genotype. This definition is very broad encompassing a variety of phenomena.
Epigenetic changes during cellular differentiation
For example, a change in phenotype of a single cell that is then passed on to its descendants qualifies as an epigenetic phenomenon. Thus it includes the various pathways of differentiation that are taken by cells during the embryonic development of an organism. Examples:
- X-inactivation — where one of the two X chromosomes in female mammals is inactivated in each cell early in development and that same chromosome remains inactivated in all the descendants of that cell.
- Imprinting — where whether a gene in a cell lineage is expressed or not depends on which parent contributed the gene.
The great stumbling block in converting differentiated cells into induced pluripotent stem cells (iPSCs) was to find ways of reversing the epigenetic changes in the differentiated cell (e.g., a skin cell) to unlock its full developmental potential. Stable changes in gene expression are brought about in two main ways:
- DNA methylation — where its cytosines are methylated. This usually represses the activity of that DNA.
- Histone modifications — where methyl, acetyl, and other groups are added to the histones in chromatin. Prominent examples:
- adding methyl groups to the #4 lysine in histone H3 ("H3K4me"). This is associated with active genes in that region of the chromatin.
- adding methyl groups to the #27 lysine in histone H3 ("HeK27me"). This is associated with gene silencing.
- epigenetic "writers": enzymes that add chemical groups to histones or DNA.
- epigenetic "erasers": enzymes that remove these groups.
- epigenetic "readers": proteins that recognize specific epigenetic modifications of histones or DNA producing a change in gene expression, e.g., increasing (or decreasing) gene transcription.