histone H3K4 methyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: S-adenosyl-L-methionine + histone H3 L-lysine (position 4) = S-adenosyl-L-homocysteine + histone H3 N6-methyl-L-lysine (position 4). This reaction is the addition of up to three methyl groups to the lysine residue at position 4 of the histone H3 protein. [PMID:12086618]

Histone H3K4 methyltransferase activity is a crucial epigenetic modification that plays a vital role in regulating gene expression. It involves the transfer of a methyl group from a donor molecule, typically S-adenosyl methionine (SAM), to the lysine 4 (K4) residue on the N-terminal tail of histone H3. This methylation event can occur at different levels, resulting in mono-, di-, or tri-methylation (H3K4me1, H3K4me2, H3K4me3). Each methylation state has distinct regulatory functions.

H3K4 methylation is primarily associated with active gene transcription. H3K4me3, the most highly methylated state, is typically found at promoters of actively transcribed genes. It recruits various chromatin remodeling complexes and transcription factors that facilitate gene activation. H3K4me2 is often found in enhancers, regulatory elements that enhance gene expression, and can also be present at promoters, contributing to the overall transcriptional activity. H3K4me1 is generally associated with poised or primed genes, indicating a potential for future transcription.

Histone H3K4 methyltransferases, also known as SET domain-containing proteins, are a family of enzymes responsible for catalyzing this methylation reaction. Some key members of this family include:

- **SET1/COMPASS complex:** This multi-protein complex is responsible for H3K4me1, H3K4me2, and H3K4me3 deposition. It is essential for developmental processes and cell fate decisions.
- **MLL complex:** This complex is involved in H3K4me3 deposition at specific genes, particularly those involved in hematopoiesis. Mutations in MLL are associated with leukemia.
- **ASH1L complex:** This complex contributes to H3K4me2 and H3K4me3 deposition, playing a role in neuronal development and differentiation.

In addition to its role in gene activation, H3K4 methylation is also implicated in various other cellular processes, including DNA replication, DNA repair, and cell cycle regulation. Dysregulation of H3K4 methylation can lead to developmental defects, cancer, and other diseases.

The precise molecular function of H3K4 methyltransferase activity is complex and involves intricate interactions between various proteins and DNA elements. This intricate interplay ultimately shapes the epigenetic landscape and plays a crucial role in regulating gene expression and cellular function.'
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Proteins (8)

Compounds (10)