Chromatin modulation by oncogenic transcription factors: new complexity, new therapeutic targets

Oncogenic transcription factors such as PML-RARalpha, RUNX1-MTG8, and others work in large part by the recruitment of inhibitors of gene transcription to target promoters leading to aberrant repression of gene expression. PML-RARalpha, an archetypal chimeric oncoprotein, was previously shown to bring complexes of histone deacetylases (HDACs), histone methyltransferases (HMTases), and DNA methyl transferases (DNMTs) to target genes. In this issue of Cancer Cell, Villa et al. show that the full complement of chromatin machinery can be commandeered by these transcription factors with the polycomb group of proteins representing the newest identified recruit.