Histone H3K4 demethylases are essential in development and differentiation.

Lysine histone methylation is one of the most robust epigenetic marks and is essential for the regulation of multiple cellular processes. The methylation of Lys4 of histone H3 seems to be of particular significance. It is associated with active regions of the genome, and in Drosophila it is catalyzed by trithorax-group proteins that have become paradigms of developmental regulators at the level of chromatin. Like other histone methylation events, H3K4 methylation was considered irreversible until the identification of a large number of histone demethylases indicated that demethylation events play an important role in histone modification dynamics. However, the described demethylases had no strictly assigned biological functions and the identity of the histone demethylases that would contribute to the epigenetic changes specifying certain biological processes was unknown. Recently, several groups presented evidence that a family of 4 JmjC domain proteins results in the global changes of histone demethylation, and in elegant studies using model organisms, they demonstrated the importance of this family of histone demethylases in cell fate determination. All 4 proteins possess the demethylase activity specific to H3K4 and belong to the poorly described JARID1 protein family.