Epigenetics

Epigenetics is the process of heritable change in gene activity despite alteration of the hosts DNA sequence, essentially causing a change in a phenotype without a change in the genotype of a host. To change the gene sequence without interfering with the DNA is accomplished by histone and DNA methylation.  Gene silencing in DNA methylation is carried out by DNA methyltransferases 1, 2 and 3a/b (DNMT1, DNMT2, DNMT3A/B). On a broad level, DNMT’s methylate the fifth carbon of cytosine residues in DNA within CG dinucleotides.

Epigenetics is the study of heritable change in gene activity despite alteration of the hosts DNA sequence.  Change in gene activity done independently of the DNA sequence is achieved by way of histone and DNA methylation.  Gene silencing in DNA methylation is carried out by DNA methyltransferases 1, 2 and 3a/b (DNMT1, DNMT2, DNMT3A/B). On a broad level, DNMTs methylate the fifth carbon of cytosine residues in DNA within CG dinucleotides.

Histones make up the main protein component of chromatin and are responsible for storing and organizing the genome in a compact yet accessible manner. In addition to storage, histones play an important role in the regulation of various cellular processes such as DNA replication, transcription, and mitosis by regulating the accessibility of DNA to various DNA-binding proteins. Simply put, chromatin exists in “open” and “closed” states.

Histones are the main protein component of chromatin and are essential for the storage and compaction of the genome. DNA wraps around histone oligomers to make up nucleosomes, the individual subunits of chromatin. By altering the accessibility of the genome, chromatin structure is important for regulating various cellular processes including replication, transcription, and DNA repair. Typically chromatin structure is influenced by post-translational modification of histone proteins at lysine and arginine residues.

DNA methylation plays a critical role the long-term silencing of transcription and is essential for processes such as embryonic development, germline differentiation, and tissue maturation.

RNA polymerase II is a large 12-subunit complex that synthesizes all mRNAs and several non-coding RNAs in eukaryotic cells. It is a DNA-dependent RNA polymerase enzyme that catalyzes transcription of DNA into RNA based on the four ribonucleoside triphosphate building blocks. RNA polymerase II is regulated through DNA-binding transcriptional regulators in both gene and cell type-specific manners.

Dnmt1 belongs to the C5-methyltransferase family that repairs cytosines in dsDNA using a nucleophilic attack mechanism. Dnmt1 is the most abundant mammalian DNA methyltransferase. It is the key methylation maintenance enzyme for both DNA replication/repair and de novo methylation during somatic cell development and differentiation.

Eukaryotic chromosomes are formed through the highly organized and structural wrapping of DNA genetic material around histone proteins into the classic "bead on a string" globular structure of nucleosomes. The histone family consists of five family members - histone H1, H2A, H2B, H3, and H4.

ZEB1 (Zinc finger E-box-binding homeobox 1) encodes a zinc finger transcription factor that represses T-lymphocyte-specific IL2-gene expression through binding to a small negative regulatory domain within the IL2 transcriptional start site (1).

Jumonji domain-containing protein 3 (JMJD3), identified as H3K27me3 demethylase, controls the expression of key regulators and markers of neurogenesis, and is required for commitment to the neural lineage. Nevertheless, the precise molecular targets of JMJD3 remain largely uncharacterized. The regulation of JMJD3 appears to be highly gene- and context- specific, suggesting interplay with specific molecules to promote fine-tuning more than the on/off alternation of methylation status.