Allele‐Specific Inhibition of Histone Demethylases

Kinetic Analysis and Inhibition Studies of Iron-Dependent Histone Demethylases

The discovery of histone demethylases.

Histone methylation is a key element of the eukaryotic epigenome. Since the discovery of the first histone demethylase (HDM) in 2004, more than 20 demethylases have been identified and characterized. They belong to either the LSD family or the JmjC family, demonstrating the reversibility of all methylation states at almost all major histone lysine methylation sites. These findings ended decades...

Developmental roles of the histone lysine demethylases.

Since the discovery of the first histone lysine demethylase in 2004, two protein families with numerous members have been identified that demethylate various histone lysine residues. Initial studies of the histone lysine demethylases focused on their in vitro enzymatic activity but, more recently, model organisms have been used to examine the roles of these enzymes in vivo. Here, we review rece...

The emerging functions of histone demethylases.

Epigenetic information refers to heritable changes in gene function that are stable between cell divisions but which is not a result of changes in the DNA sequence. Part of the epigenetic mechanism has been ascribed to modifications of histones or DNA that affects the transcription of specific genes. In this context, post-translational modifications of histone tails, in particular methylation o...

Interfering with histone demethylases in HSCs.

S tem cells are governed by epigenetic mechanisms that can either help maintain the necessary gene expression programs to preserve the stem cell state or ensure the establishment of new cell-specific expression programs during differentiation. One important level of epigenetic control originates from histone modifications such as methylation or acetylation. These modifications can be associated...