Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a
histone methyltransferase
Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residue ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that in humans is encoded by the ''EHMT2''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
G9a catalyzes the mono- and di-methylated states of
histone H3
Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a stri ...
at
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated &minu ...
residue 9 (i.e.,
H3K9me1 and
H3K9me2) and lysine residue 27 (
H3K27me1 and
HeK27me2).
Function
A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described.
G9a and
G9a-like protein, another histone-lysine N-methyltransferase, catalyze the synthesis of
H3K9me2, which is a
repressive mark.
G9a is an important control mechanism for
epigenetic regulation within the
nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...
(NAcc);
reduced G9a expression in the NAcc plays a central role in mediating the development of an
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...
.
G9a opposes increases in
ΔFosB
Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene.
The FOS gene family consists of four members: FOS, F ...
expression via
H3K9me2 and is suppressed by ΔFosB.
G9a exerts opposite effects to that of ΔFosB on drug-related behavior (e.g.,
self-administration
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
In animal experiment ...
) and synaptic remodeling (e.g.,
dendritic arborization – the development of additional tree-like
dendritic branches and
spines) in the nucleus accumbens, and therefore opposes ΔFosB's function as well as increases in its expression.
G9a and ΔFosB share many of the same gene targets.
Figure 4: Epigenetic basis of drug regulation of gene expression
/ref> In addition to its role in the nucleus accumbens, G9a play a critical role in the development and the maintenance of neuropathic pain.dorsal root ganglia
A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dorsa ...
. This transcriptomic change reprograms the sensory neurons to a hyperexcitable state leading to mechanical pain hypersensitivity. [
]
Interactions
EHMT2 has been shown to interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with KIAA0515 and the prostate tissue associated homeodomain protein NKX3.1.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
{{PDB Gallery, geneid=10919