In:
Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 26, No. 15 ( 2019-07-25), p. 2748-2785
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.
Type of Medium:
Online Resource
ISSN:
0929-8673
DOI:
10.2174/0929867325666180706105903
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2019
SSG:
15,3
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