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Context-Dependent Functions of KDM6 Lysine Demethylases in Physiology and Disease. | LitMetric

Context-Dependent Functions of KDM6 Lysine Demethylases in Physiology and Disease.

Adv Exp Med Biol

Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Center for Medical Genetics, Ghent University, Medical Research Building 2 (MRB2), Entrance 38, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

Published: September 2023

AI Article Synopsis

Article Abstract

Histone lysine methylation is a major epigenetic modification that participates in several cellular processes including gene regulation and chromatin structure. This mark can go awry in disease contexts such as cancer. Two decades ago, the discovery of histone demethylase enzymes thirteen years ago sheds light on the complexity of the regulation of this mark. Here we address the roles of lysine demethylases JMJD3 and UTX in physiological and disease contexts. The two demethylases play pivotal roles in many developmental and disease contexts via regulation of di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) in repressing gene expression programs. JMJD3 and UTX participate in several biochemical settings including methyltransferase and chromatin remodeling complexes. They have histone demethylase-dependent and -independent activities and a variety of context-specific interacting factors. The structure, amounts, and function of the demethylases can be altered in disease due to genetic alterations or aberrant gene regulation. Therefore, academic and industrial initiatives have targeted these enzymes using a number of small molecule compounds in therapeutic approaches. In this chapter, we will touch upon inhibitor formulations, their properties, and current efforts to test them in preclinical contexts to optimize their therapeutic outcomes. Demethylase inhibitors are currently used in targeted therapeutic approaches that might be particularly effective when used in conjunction with systemic approaches such as chemotherapy.

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http://dx.doi.org/10.1007/978-3-031-38176-8_7DOI Listing

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