H3K9me2

H3K9me2

Methylation of lysine

H3K9me2 refers to the dimethylation of the ninth lysine residue on the histone H3 protein. This post-translational modification is a key epigenetic marker involved in the regulation of gene expression, chromatin structure, and genome stability.

Structure and Function

Histone proteins, including histone H3, are essential components of chromatin, the complex of DNA and protein found in the nucleus of eukaryotic cells. The N-terminal tail of histone H3 can undergo various post-translational modifications, such as methylation, acetylation, and phosphorylation. These modifications influence chromatin dynamics and gene expression.

H3K9me2 is specifically the addition of two methyl groups to the lysine residue at position 9 of the histone H3 tail. This modification is catalyzed by specific histone methyltransferases, such as G9a and GLP. H3K9me2 is generally associated with transcriptional repression and the formation of heterochromatin, a tightly packed form of DNA.

Biological Role

H3K9me2 plays a crucial role in maintaining genomic stability and regulating gene expression. It is involved in:

• Heterochromatin Formation: H3K9me2 is a marker for heterochromatin, which is transcriptionally inactive. This modification helps recruit proteins that compact chromatin and silence gene expression.

• Gene Silencing: By promoting a closed chromatin conformation, H3K9me2 represses the transcription of genes, particularly those that need to be silenced during development or in response to environmental signals.

• DNA Methylation: H3K9me2 is often found in regions of the genome that are also methylated at the DNA level, suggesting a coordinated mechanism of gene silencing.

Enzymes Involved

The addition of methyl groups to H3K9 is mediated by histone methyltransferases, such as:

• G9a (EHMT2): A major enzyme responsible for H3K9 dimethylation in euchromatin.
• GLP (EHMT1): Works in conjunction with G9a to establish H3K9me2 marks.

The removal of methyl groups from H3K9me2 is carried out by histone demethylases, such as:

• KDM3A (JMJD1A): A demethylase that specifically removes methyl groups from H3K9me2, converting it back to H3K9me1 or unmethylated H3K9.

Clinical Significance

Alterations in H3K9me2 levels have been implicated in various diseases, including cancer. Abnormal H3K9me2 patterns can lead to inappropriate gene silencing or activation, contributing to tumorigenesis. Understanding the regulation of H3K9me2 is therefore important for developing therapeutic strategies targeting epigenetic modifications.

Related Pages

• Histone modification
• Epigenetics
• Chromatin
• Gene expression
• Histone methyltransferase