Polycomb group proteins and long-range gene regulation.

Genome regulation takes place at different hierarchically interconnected levels: the DNA sequence level, the chromatin level, and the three-dimensional (3D) organization of the nucleus. Polycomb group (PcG) proteins are silencers that regulate transcription at all these three levels. They are targeted to specific sequences in the genome, contributing to maintain cellular identity. Recent research reveals that PcG proteins may be important actors at the level of the nuclear 3D structure. Here, we discuss our current knowledge of how PcG proteins regulate transcription across the three mentioned levels, and in particular their possible role in regulation of remote genes. We suggest the possibility that PcG proteins establish 3D networks of chromatin contacts as a mechanism to orchestrate gene expression.