The transcription factor code: a beacon for histone methyltransferase docking

Histone methylation is required for the establishment and maintenance of gene expression patterns that determine cellular identity, and its perturbation often leads to aberrant development and disease. Recruitment of histone methyltransferases (HMTs) to gene regulatory elements (GREs) of developmental genes is important for the correct activation and silencing of these genes, but the drivers of this recruitment are largely unknown. Here we propose that lineage-instructive transcription factors (Lin-TFs) act as general recruiters of HMT complexes to cell type-specific GREs through protein-protein interactions. We also postulate that the specificity of these interactions is dictated by Lin-TF post-translational modifications (PTMs), which act as a 'transcription factor code' that can determine the directionality of cell fate decisions during differentiation and development.