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Histone methylation is a dynamic process that contributes to the control of gene expression by influencing chromatin structure. Since their initial discovery 20 years ago, histone demethylases have been shown to play a critical role in histone methylation and thus developmental, physiological, and pathological processes. Dysregulation of this class of enzymes has been linked to nearly all types of cancers but their complex interactions and elusive functions continue to impede therapeutic development. Here, we explore the demethylase family, its sub-families, and the great efforts to identify novel, specific inhibitors to understand their complex biological functions and therapeutic potential.

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