Taking LSD1 to a new high

Histone modifications mediate changes in gene expression by altering the underlying chromatin structure or by serving as a binding platform to recruit other proteins. One such modification, histone methylation, was thought to be irreversible until last year when Shi and coworkers broke new ground with their discovery of a lysine-specific histone demethylase (LSD1). They showed that LSD1, a nuclear amine oxidase homolog, is a bona fide histone H3 lysine 4 demethylase (Shi et al., 2004). Now, a new study from Shi et al. (2005) published in a recent issue of Molecular Cell, together with two studies recently published by Metzger et al. (2005) and Lee et al. (2005) in Nature, reveal that LSD1's specificity and activity is in fact regulated by associated protein cofactors.