Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA sequence, but instead by the chromatin organization and histone variants. Once established, the centromere organization and functions remain stably inherited through several cell divisions.

Histones are central to epigenetic inheritance

In the nucleosome, both DNA and histones are chemically modified. DNA is methylated at cytosine residues, and histones are methylated, acetylated, or phosphorylated. Each of these modifications constitutes a signal called histone code. Recent advances highlight methylation as a bona fide epigenetic mark, and chromatin complexity as the primary carrier of epigenetic marks. The presence of histone variants at specific locations and time increases the complexity of chromatin organization. For example, the histone H3 variant CENP-A is incorporated into a nucleosome in a DNA synthesis-independent manner, resulting in an unusually stable nucleosome.

Inheritance of histones

The DNA methylation, deposition of histones on DNA strands, and post-translational modifications of histones or histone code are connected to replication machinery. PCNA, a DNA processivity factor, is the vital protein that links DNA replication with the inheritance of epigenetic marks. At the replication fork, the nucleosomes are displaced such that H2A-H2B dimers are entirely removed from the replication fork. The parental H3-H4 tetramers are then distributed to daughter strands followed by the placement of newly synthesized histone subunits on parental histones to complete the nucleosomes.