Histone-modifying enzymes

[1][2] To safely store the eukaryotic genome, DNA is wrapped around four core histone proteins (H3, H4, H2A, H2B), which then join to form nucleosomes.

These nucleosomes further fold together into highly condensed chromatin, which renders the organism's genetic material far less accessible to the factors required for gene transcription, DNA replication, recombination and repair.

The positive charge on a histone is always neutralized upon acetylation, creating euchromatin which increases transcription and expression of the target gene.

Histone methylation is responsible for either activation or repression of genes, depending on the target site, and plays an important role in development and learning.

[citation needed] Additionally, the phosphorylation of histones has been found to play a role in DNA repair and chromatin condensation during cell division.

The addition and removal of GlcNAc groups are performed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) respectively.

[28] ADP-ribosylation (ADPr) defines the addition of one or more adenosine diphosphate ribose (ADP-ribose) groups to a protein.

[29] ADPr is an important mechanism in gene regulation that affects chromatin organization, the binding of transcription factors, and mRNA processing through poly-ADP ribose polymerase (PARP) enzymes.

PARP-1 binds histones near the axis where DNA enters and exits the nucleosome and additionally interacts with numerous chromatin-associated proteins which allow for indirect association with chromatin.

[36] Fpr4 is the prolyl isomerase enzyme (PPIase) which converts the amino acid proline (P) on histones between the cis and trans conformations.

Conversely, the trans position of P38 promotes a more open histone conformation, allowing for K36 methylation and leading to an increase gene transcription.

[36] Alterations in the functions of histone-modifying enzymes deregulate the control of chromatin-based processes, ultimately leading to oncogenic transformation and cancer.

[40] Vitamin B12 deficiency in mice has been shown to alter expression of histone modifying enzymes in the brain, leading to behavioral changes and epigenetic reprogramming.