The emerging roles for histone demethylases in the modulation of signaling pathways.

Since their discovery in 2004, histone demethylases have emerged as key regulators of chromatin. Recent studies have started to reveal the interconnections between histone demethylases and signaling pathways, suggesting that this interplay drives fundamental biological processes. Here, we summarize the different families and subfamilies of histone demethylases and the insights into the biological roles of these enzymes that have been provided by the analysis of mutant animals. We then review recent work linking demethylases and signaling pathways. These studies suggest that demethylase activities are a component of the critical connections that enable environmental signals to modulate the epigenetic landscape of a cell. A greater mechanistic understanding of the network of signals that control chromatin states during normal cellular processes, together with a better understanding of the ways that epigenetic alterations lead to uncontrolled cell proliferation, might help in the design of effective tools for cancer therapy.