# Chromatin folding by the Polycomb group proteins and its elusive role in epigenetic repression

## TL;DR

This paper reviews how Polycomb proteins repress genes through chromatin folding and discusses how this process might contribute to epigenetic repression.

## Contribution

The paper provides a review of chromatin folding mechanisms by Polycomb proteins and questions traditional models of gene repression.

## Key findings

- Genes repressed by the Polycomb system show increased chromatin folding compared to inactive genes.
- Chromatin compaction driven by PRC1-H3K27me3 interactions is modest and dynamic.
- The role of chromatin folding in epigenetic repression remains an open question.

## Abstract

The Polycomb system epigenetically represses selected developmental genes to enforce gene expression programs of differentiated cells. The system requires the coordinated action of dozens of structurally unrelated proteins assembled in two evolutionarily conserved polycomb repressive complexes, PRC1 and PRC2. Genes repressed by the Polycomb system are enriched in histone H3 trimethylated at lysine 27 (H3K27me3), an epigenetic mark that propagates the repressed state after DNA replication. Despite the impressive progress in dissecting molecular functions of the Polycomb group proteins, the fundamental questions of how the Polycomb system represses transcription or how the H3K27me3 mark is translated to benefit the repression are still open. Multiple observations indicate that the binding of PRC1, PRC2, and elevated H3K27me3 correlate with changes in the chromatin structure of target genes, which may be integral for the associated epigenetic repression. In this Review, we summarize our current understanding of these observations. We discuss the chromatin folding inside the loci repressed by the Polycomb system, consider molecular processes causing it and reflect upon its possible impact on transcription and epigenetic memory of the repressed state.

Genes repressed by the Polycomb system display greater chromatin folding compared to ‘regular’ inactive genes. The associated chromatin compaction, driven by PRC1‐H3K27me3 interactions, is modest and dynamic. This questions traditional models where Polycomb proteins repress transcription by sheltering genes from transcriptional activators. How such dynamic chromatin folding helps epigenetic repression or whether it is an ineffectual byproduct of molecular interactions within the Polycomb system are important open questions.