Chromatin Sampling—An Emerging Perspective on Targeting Polycomb Repressor Proteins

Polycomb group (PcG) repressor proteins play a central role in gene regulation through differentiation and development, conferring repressive chromatin configurations at target gene promoters through their inherent histone modification activities. Recruitment of Polycomb repressor proteins to defined targets has been attributed to instructive mechanisms in which sequence-specific binding proteins and/or noncoding RNAs interact biochemically with the major Polycomb repressive complexes and thus define their sites of action. Here we highlight that this viewpoint is increasingly incompatible with experimental observations. We propose an alternative perspective based on the concept that Polycomb recruitment is responsive rather than instructive. Specifically, we suggest that Polycomb complexes sample permissive chromatin sites, and through positive feedback mechanisms, accumulate at those sites lacking antagonistic chromatin modifying activities linked to ongoing transcription.