Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact

Abstract

Histone lysine methylation has emerged as a critical player in the regulation of gene expression, cell cycle, genome stability, and nuclear architecture. Over the past decade, a tremendous amount of progress has led to the characterization of methyl modifications and the lysine methyltransferases (KMTs) and lysine demethylases (KDMs) that regulate them. Here, we review the discovery and characterization of the KMTs and KDMs and the methyl modifications they regulate. We discuss the localization of the KMTs and KDMs as well as the distribution of lysine methylation throughout the genome. We highlight how these data have shaped our view of lysine methylation as a key determinant of complex chromatin states. Finally, we discuss the regulation of KMTs and KDMs by proteasomal degradation, posttranscriptional mechanisms, and metabolic status. We propose key questions for the field and highlight areas that we predict will yield exciting discoveries in the years to come.

Epigenetic modification in chromatin machinery and its deregulation in pediatric brain tumors: Insight into epigenetic therapies

“…distribution of histone methylation and of related enzymes can also change during the cell cycle, affecting replication timing (reviewed in 20 ). Of note, the description of these histone posttranslational modifications above is not exhaustive as, for example, phosphorylation also occurs and impacts transcription.…”

“…Modulation of the epigenetic regulators, known as "readers," structurally diverse proteins that recognize and bind to covalent modifications of chromatin, has recently emerged as a therapeutic strategy in the treatment of brain cancer and also of other cancers (reviewed in. 6,20,[68][69][70][71][72][73][74] ).…”

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

“…Whereas asymmetric methylation is often associated with active transcription, symmetric methylation can drive repression and silencing. Histone methylation has been extensively studied and covered by many excellent reviews [209][210][211][212][213][214].…”

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

“…Experimental studies reveal that at least some of the histone post-translational modification patterns are inheritable, which is called histone epigenetics memory (3,4). In the past few years, different groups had discovered multiple enzymes regulating the histone modification dynamics (3,5). The so-called 'histone code' proposal, although still under debate, has drawn extensive attention from the field (6).…”