Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.
The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer.
Cloos
Paul A C
PA
Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark. paul.cloos@bric.dk
Christensen
Jesper
J
Agger
Karl
K
Helin
Kristian
K
D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010089:Oxidoreductases, N-Demethylating / Q000145:classification / Q000378:metabolism*; D010802:Phylogeny
D006657:Histones; D010089:Oxidoreductases, N-Demethylating