Histone-lysine N-methyltransferase 2 (KMT2) complexes - a new perspective.

Area of Science:

• Epigenetics
• Molecular Biology
• Biochemistry

Background:

• Histone H3 Lys4 (H3K4) methylation by the Histone-Lysine N-Methyltransferase 2 (KMT2) protein family is crucial for gene expression.
• KMT2 proteins function in COMPASS complexes, vital for development, with mutations linked to cancers and neurodevelopmental disorders.
• The established role of KMT2s is H3K4 methylation, creating a permissive chromatin state for gene expression.

Purpose of the Study:

• To review the noncanonical activities of KMT2 complexes beyond their established role in H3K4 methylation.
• To highlight the involvement of KMT2s in processes independent of their catalytic methylation activity.
• To explore the implications of these novel functions for understanding development, disease, and therapeutic strategies.

Main Methods:

• Literature review of recent findings on KMT2 complex functions.
• Analysis of studies investigating noncatalytic roles of KMT2s.
• Synthesis of research on KMT2s' involvement in DNA damage response, cell division, and metabolism.

Main Results:

• KMT2s exhibit noncatalytic functions, including roles in DNA damage response, cell division, and metabolic activities.
• These enzymes can methylate non-histone substrates, indicating broader substrate specificity.
• KMT2s also participate in methylation-dependent DNA damage response pathways.

Conclusions:

• KMT2 complexes possess diverse, noncanonical functions beyond histone methylation.
• These newly identified roles in cellular processes are critical for development and disease.
• Understanding these noncanonical activities is essential for developing novel epigenome-targeting therapies.