A long-standing controversy in the field is the mode by which chromatin-remodelling complexes are targeted to their site of action, which is key to achieving biological specificity. Because most remodellers lack sequence-specific DNA-binding motifs, the predominant view is that they are recruited by way of transient interactions with transcription factors and with DNA-binding proteins that recognize specific DNA sequences. From this viewpoint, in the context of development, remodellers would have an accessory role rather than an instructive role in shaping the transcriptional program and therefore the lineage outcome of a cell. However, there is also ample evidence that, in some cases, remodellers are pretargeted to their sites of action, either by histone modifications or by unknown mechanisms, and that they prepare the target site for binding by transcription factors91. Such examples suggest that remodellers have an instructive role in determining the ability of a particular genome to respond transcriptionally to signals that lead to recruitment of a transcription factor or DNA-binding factor to chromatin. If this is true, the obvious questions are how remodellers recognize their targets and whether this targeting is required for a cell to respond specifically to developmental cues during lineage commitment.
