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The main mechanisms that control epigenetic processes include DNA methylation, histone modifications, histone variant incorporation, chromatin remodeling, and miRNA‐regulated gene expression. Methylation takes place on both lysine and arginine residues. This chapter discusses the dynamic nature of histone lysine methylation and demethylation, explaining how these processes impact hormonal gene regulation. Some of these enzymes also act on nonhistone proteins; consequently, they are also known as lysine methyltransferases (KMTs) and lysine demethylases (KDMs). In hormone signaling, nuclear receptors (NRs) sense and bind ligands such as steroid or thyroid hormones and other small molecules that are important for metabolism, development, and homeostasis. The chapter focuses on how the histone lysine methylation‐regulating enzymes of the KMT and KDM families collaborate with NRs …