The article provides a comprehensive review of histone lysine methylation, focusing on the enzymes responsible for its regulation and the biological roles it plays. Histone modifications, particularly lysine methylation, are crucial for various cellular processes such as gene expression, DNA replication, and chromatin structure. The review highlights the importance of methyltransferases ('writers') and demethylases ('erasers') in maintaining the balance of histone methylation levels. It also discusses the 'readers' that recognize specific methyl-lysines, which can influence gene expression and cellular functions. The article delves into the detailed mechanisms of H3K4, H3K9, H3K27, H3K36, and H3K79 methylation, including the enzymes involved, their substrate specificity, and the biological consequences of their misregulation. For example, H3K4 methylation is associated with active transcription, while H3K9 methylation marks silenced transcription and heterochromatin structure. H3K27 methylation is a hallmark of transcriptional repression, and H3K36 methylation plays a role in preventing abortive transcription initiation and regulating alternative splicing. The review also explores the clinical implications of histone lysine methylation, noting that misregulation of these modifications has been linked to various diseases, including cancers and developmental disorders. The development of inhibitors targeting histone lysine methyltransferases and demethylases has shown promising results in clinical trials, highlighting the potential of this approach in disease treatment. Overall, the article emphasizes the need for a deeper understanding of histone lysine methylation to elucidate complex biological processes and improve disease treatments.The article provides a comprehensive review of histone lysine methylation, focusing on the enzymes responsible for its regulation and the biological roles it plays. Histone modifications, particularly lysine methylation, are crucial for various cellular processes such as gene expression, DNA replication, and chromatin structure. The review highlights the importance of methyltransferases ('writers') and demethylases ('erasers') in maintaining the balance of histone methylation levels. It also discusses the 'readers' that recognize specific methyl-lysines, which can influence gene expression and cellular functions. The article delves into the detailed mechanisms of H3K4, H3K9, H3K27, H3K36, and H3K79 methylation, including the enzymes involved, their substrate specificity, and the biological consequences of their misregulation. For example, H3K4 methylation is associated with active transcription, while H3K9 methylation marks silenced transcription and heterochromatin structure. H3K27 methylation is a hallmark of transcriptional repression, and H3K36 methylation plays a role in preventing abortive transcription initiation and regulating alternative splicing. The review also explores the clinical implications of histone lysine methylation, noting that misregulation of these modifications has been linked to various diseases, including cancers and developmental disorders. The development of inhibitors targeting histone lysine methyltransferases and demethylases has shown promising results in clinical trials, highlighting the potential of this approach in disease treatment. Overall, the article emphasizes the need for a deeper understanding of histone lysine methylation to elucidate complex biological processes and improve disease treatments.