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. Lineage-instructive transcription factors (Lin-TFs) are able to drive cell fate changes by binding to sequence-specific motifs in gene regulatory elements (GREs). Histone methyltransferases (HMTs) decorate histones at different GREs in different cell types throughout development, regulating lineage-restricted gene activation and silencing. Several mechanisms for HMT recruitment to lineage-specific GREs have been described, but there is no clear consensus in the field. Time-resolved analysis shows that transcription factor binding often precedes histone modification changes in the neighboring nucleosomes. Lin-TFs can interact with HMT complexes. Lin-TFs are targets of a large number of modifying enzymes. Some of the resulting PTMs have been reported to modulate interactions of Lin-TFs with other proteins. [ABSTRACT FROM AUTHOR]