Histone demethylation and steroid receptor function in cancer

Steroid receptors recruit various cofactors to form multi-protein complexes which locally alter chromatin structure and control DNA accessibility in order to regulate gene transcription. Some of these factors are enzymes that add or remove histone marks in the vicinity of regulatory regions of target genes. Numerous histone modifications added by specific writer enzymes and removed by eraser enzymes have been identified. Histone methylation is a modification with a complex outcome, as it can lead to gene activation or repression, depending on the modified residue and the context. Methylation marks are added by different enzyme families displaying exquisite substrate specificity. Lysine methylation is reversible and two different demethylase families have been identified in humans, the Jumonji C and the lysine-specific demethylase families. A regulatory role of histone demethylases in fine-tuning the function of steroid receptors, especially the androgen receptor and estrogen receptor, has emerged in recent years. This is mostly inferred from in vitro studies, but more recently first in vivo data have further supported this concept. This and the deregulated expression observed for several histone demethylases suggest a role in tumours such as prostate and breast cancer.