Histone lysine methylation modifiers controlled by protein stability

Abstract

Histone lysine methylation is pivotal in shaping the epigenetic landscape and is linked to cell physiology. Coordination of the activities of multiple histone lysine methylation modifiers, namely, methyltransferases and demethylases, modulates chromatin structure and dynamically alters the epigenetic landscape, orchestrating almost all DNA-templated processes, such as transcription, DNA replication, and DNA repair. The stability of modifier proteins, which is regulated by protein degradation, is crucial for their activity. Here, we review the current knowledge of modifier-protein degradation via specific pathways and its subsequent impact on cell physiology through epigenetic changes. By summarizing the functional links between the aberrant stability of modifier proteins and human diseases and highlighting efforts to target protein stability for therapeutic purposes, we aim to promote interest in defining novel pathways that regulate the degradation of modifiers and ultimately increase the potential for the development of novel therapeutic strategies. Histone modifications, such as methylation, are key in controlling gene expression by changing the structure of chromatin, the DNA and protein mix in our cells’ nucleus. This study investigates how the stability of histone lysine methylation modifiers—enzymes that add or remove methyl groups from histones—is managed. It’s a study aimed at understanding the delicate balance of these modifiers in the cell. The researchers studied various cell processes, including the ubiquitin-proteasome system, and post-translational modifications, that affect the stability of these enzymes. The results show changing the stability of these modifiers can alter histone methylation patterns, suggesting new ways to target diseases like cancer. Researchers conclude that understanding the control of enzyme stability offers a promising path for developing therapies that can correct abnormal gene expression by targeting the enzymes responsible for histone modifications. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.