Histone methylation

Histone methylation is a process by which methyl groups are transferred to amino acids of histone proteins that make up nucleosomes, which the DNA double helix wraps around to form chromosomes. Methylation of histones can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated, and how many methyl groups are attached. Methylation events that weaken chemical attractions between histone tails and DNA increase transcription, because they enable the DNA to uncoil from nucleosomes so that transcription factor proteins and RNA polymerase can access the DNA. This process is critical for the regulation of gene expression that allows different cells to express different genes.

Histone methylation, as a mechanism for modifying chromatin structure is associated with stimulation of neural pathways known to be important for formation of long-term memories and learning. Animal models have shown methylation and other epigenetic regulation mechanisms to be associated with conditions of aging, neurodegenerative diseases, and intellectual disability (Rubinstein–Taybi Syndrome, X-linked mental retardation). This modification alters the properties of the nucleosome and affects its interactions with other proteins, particularly in regards to gene transcription processes.

The fundamental unit of chromatin, called a nucleosome, contains DNA wound around a protein octamer. This octamer consists of two copies each of four histone proteins: H2A, H2B, H3, and H4. Each one of these proteins has a tail extension, and these tails are the targets of nucleosome modification by methylation. DNA activation or inactivation is largely dependent on the specific tail residue methylated and its degree of methylation. Histones can be methylated on lysine (K) and arginine (R) residues only, but methylation is most commonly observed on lysine residues of histone tails H3 and H4. The tail end furthest from the nucleosome core is the N-terminal (residues are numbered starting at this end). Common sites of methylation associated with gene activation include H3K4, H3K48, and H3K79. Common sites for gene inactivation include H3K9 and H3K27. Studies of these sites have found that that methylation of histone tails at different residues serve as markers for the recruitment of various proteins or protein complexes that serve to regulate chromatin activation or inactivation.

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