Covalent modification of histones on chromatin is a dynamic mechanism by which various nuclear processes are regulated. Methylation of histone H3 on lysine 4 (H3K4) implemented by the macromolecular complex COMPASS and its related complexes is associated with transcriptionally active regions of chromatin. Enzymes that catalyze H3K4 methylation were initially characterized genetically as regulators of Hox loci, long before their catalytic functions were recognized. Since their discovery, genetic and biochemical studies of H3K4 methylases and demethylases have provided important mechanistic insight into the role of H3K4 methylation in HOX gene regulation during development.
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