The orchestrated organization of epigenetic factors that control
chromatin dynamism, including DNA methylation, histone marks, non-coding RNAs (ncRNAs) and chromatin-remodeling
proteins, is essential for the proper function of tissue homeostasis, cell identity and development. Indeed, deregulation of epigenetic profiles has been described in several human pathologies, including complex diseases (such as
cancer, cardiovascular and neurological
diseases), metabolic pathologies (
type 2 diabetes and
obesity) and
imprinting disorders. Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanism, such as
DNA methyltransferases, methyl-binding domain
proteins,
histone deacetylases,
histone methylases and members of the SWI/SNF family of
chromatin remodelers are linked to human disorders, including Immunodeficiency Centromeric instability Facial syndrome 1,
Rett syndrome,
Rubinstein-Taybi syndrome,
Sotos syndrome or
alpha-thalassemia/mental retardation X-linked syndrome, among others. As new members of the epigenetic machinery are described, the number of human syndromes associated with epigenetic alterations increases. As recent examples, mutations of
histone demethylases and members of the
non-coding RNA machinery have recently been associated with
Kabuki syndrome, Claes-Jensen
X-linked mental retardation syndrome and
Goiter syndrome. In this review, we describe the variety of germline mutations of epigenetic modifiers that are known to be associated with human disorders, and discuss the therapeutic potential of epigenetic drugs as
palliative care strategies in the treatment of such disorders.