Looping specificity of Polycomb response elements requires GAF and a combination of looping factors that could form a code

Polycomb Response Elements (PREs) are specialized tethering elements that mediate chromatin loops and are bound by transcription factors (TFs) like GAGA-associated factor (GAF), contributing to the recruitment of Polycomb group (PcG) proteins. While both PcG proteins and GAF have been implicated in looping, their specific roles and the mechanisms of loop specificity remain unresolved.

Using genome-wide and locus-specific approaches, we show that high GAF occupancy is required for chromatin looping and gene regulation. However, GAF alone cannot establish loops without additional factors. Surprisingly, PRE looping does not require Polycomb repressive complex 1 (PRC1) or the repressive histone mark H3K27me3.