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.
Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma
