KDM2A

KDM2A (Lysine-specific demethylase 2A), also known as FBXL11 (F-box and leucine-rich repeat protein 11), is a protein that in humans is encoded by the KDM2A gene. This enzyme is part of the Jumonji C domain-containing (JmjC) family of demethylases, which are involved in the removal of methyl groups from lysine residues on histone proteins. The demethylation of histones by KDM2A plays a crucial role in the regulation of gene expression, impacting various biological processes including cell cycle regulation, DNA repair, and development.

Function

KDM2A is a histone demethylase that specifically demethylates 'Lys-36' and 'Lys-4' of histone H3, thereby playing a central role in histone code. It does not demethylate histone H3 'Lys-9' or 'Lys-27', or histone H4. KDM2A demethylation of 'Lys-36' leads to the repression of transcriptional initiation, while demethylation of 'Lys-4' is associated with the activation of gene expression. Through these actions, KDM2A is involved in the regulation of chromatin structure and gene expression, influencing cellular processes such as differentiation and proliferation.

Clinical Significance

Alterations in the expression or function of KDM2A have been implicated in the development of various cancers. Overexpression of KDM2A has been observed in certain types of leukemia and solid tumors, where it may contribute to the oncogenic process by altering the expression of genes involved in cell cycle regulation and apoptosis. Conversely, loss of KDM2A expression has been associated with the progression of other cancers, suggesting a complex role in tumorigenesis that may be context-dependent.

Genomics

The KDM2A gene is located on human chromosome 11q13.2. It spans approximately 29 kb and consists of multiple exons. The gene encodes a protein of 1,261 amino acids, which contains a JmjC domain responsible for its demethylase activity, as well as an F-box domain, which is involved in protein-protein interactions.

Interactions

KDM2A has been shown to interact with various proteins, including components of the polycomb repressive complex 2 (PRC2), linking it to the regulation of gene expression through both histone demethylation and polycomb-mediated repression. Additionally, KDM2A interacts with DNA methyltransferases (DNMTs), suggesting a role in coordinating the interplay between histone and DNA methylation states.

Research Directions

Research on KDM2A continues to explore its biological functions and implications in disease. Studies are investigating the enzyme's potential as a therapeutic target in cancers where its expression or activity is dysregulated. Furthermore, the role of KDM2A in other diseases and its potential interactions with non-histone proteins are areas of active investigation.

See Also

• Histone demethylase
• Epigenetics
• Chromatin
• Gene expression