MLL3

MLL3 (Mixed Lineage Leukemia 3), also known as KMT2C (lysine methyltransferase 2C), is a gene that encodes a member of the SET domain-containing family of histone methyltransferases. MLL3 plays a critical role in the regulation of gene expression through the methylation of histone H3 on lysine 4 (H3K4), a process that is essential for epigenetic modulation of gene activity. This enzyme is involved in the development and maintenance of various biological processes and has been implicated in the pathogenesis of several types of cancer, including leukemia.

Function

MLL3 functions as a part of a larger protein complex known as COMPASS (COMplex of Proteins Associated with Set1), which is involved in the methylation of histone H3 at lysine 4 (H3K4me). This modification is a hallmark of actively transcribed genes. MLL3 specifically contributes to the monomethylation and dimethylation of H3K4 (H3K4me1 and H3K4me2), which are marks associated with enhancer regions of the DNA. By modifying histones, MLL3 plays a crucial role in the regulation of gene expression, affecting processes such as cell differentiation, development, and DNA repair.

Genetic Alterations and Disease Association

Alterations in the MLL3 gene, including mutations and deletions, have been identified in a variety of human cancers. These genetic changes can lead to the dysregulation of gene expression, contributing to the development and progression of cancer. For example, mutations in MLL3 have been found in cases of colorectal cancer, breast cancer, and non-Hodgkin lymphoma, among others. The loss of MLL3 function due to these mutations can result in the aberrant activation or repression of target genes, promoting oncogenesis.

Clinical Significance

Given its role in cancer, MLL3 is considered a potential target for therapeutic intervention. Understanding the mechanisms by which MLL3 mutations contribute to cancer can aid in the development of targeted therapies. For instance, drugs that can modulate the enzymatic activity of MLL3 or its interactions within the COMPASS complex may offer new avenues for cancer treatment.

Research Directions

Research on MLL3 continues to uncover its complex role in gene regulation and its implications for human disease. Studies are exploring the full spectrum of MLL3's biological functions, its interactions with other proteins and molecules within the cell, and how its activity is regulated. Additionally, the development of animal models and cell-based systems that mimic human mutations in MLL3 is crucial for advancing our understanding of its role in disease and for testing potential therapeutic strategies.