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Epigenetic Metalloenzymes

[ Vol. 26 , Issue. 15 ]

Author(s):

Christophe Blanquart, Camille Linot, Pierre-François Cartron, Daniela Tomaselli, Antonello Mai and Philippe Bertrand*   Pages 2748 - 2785 ( 38 )

Abstract:


Epigenetics controls the expression of genes and is responsible for cellular phenotypes. The fundamental basis of these mechanisms involves in part the post-translational modifications (PTMs) of DNA and proteins, in particular, the nuclear histones. DNA can be methylated or demethylated on cytosine. Histones are marked by several modifications including acetylation and/or methylation, and of particular importance are the covalent modifications of lysine. There exists a balance between addition and removal of these PTMs, leading to three groups of enzymes involved in these processes: the writers adding marks, the erasers removing them, and the readers able to detect these marks and participating in the recruitment of transcription factors. The stimulation or the repression in the expression of genes is thus the result of a subtle equilibrium between all the possibilities coming from the combinations of these PTMs. Indeed, these mechanisms can be deregulated and then participate in the appearance, development and maintenance of various human diseases, including cancers, neurological and metabolic disorders. Some of the key players in epigenetics are metalloenzymes, belonging mostly to the group of erasers: the zinc-dependent histone deacetylases (HDACs), the iron-dependent lysine demethylases of the Jumonji family (JMJ or KDM) and for DNA the iron-dependent ten-eleven-translocation enzymes (TET) responsible for the oxidation of methylcytosine prior to the demethylation of DNA. This review presents these metalloenzymes, their importance in human disease and their inhibitors.

Keywords:

DNMT, epigenetic, HDAC, TET, metalloenzymes, PTM.

Affiliation:

CRCINA, INSERM, Universite d'Angers, Universite de Nantes, Nantes, CRCINA, INSERM, Universite d'Angers, Universite de Nantes, Nantes, CRCINA, INSERM, Universite d'Angers, Universite de Nantes, Nantes, Department of Chemistry and Technologies of Drugs, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Department of Chemistry and Technologies of Drugs, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Institut de Chimie des Milieux et Materiaux de Poitiers, UMR CNRS 7285, 4 rue Michel Brunet, TSA 51106, B27, 86073, Poitiers cedex 09



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