Know when to fold ’em: Polycomb complexes in oncogenic 3D genome regulation
Chromatin organization is tightly controlled in both space and time through coordinated processes that give rise to three-dimensional (3D) structures, such as topologically associating domains (TADs), chromatin loops, and Polycomb Bodies. These structures are closely tied to the regulation of transcription, and disruptions in these processes are often implicated in cancer and developmental disorders. One notable oncogenic alteration of the 3D genome involves the recurrent dysregulation of Polycomb Group Complex (PcG) functions. Such dysregulation can arise from genetic mutations, gene amplifications, or deletions affecting PcG protein-coding genes.
PcG complexes are evolutionarily conserved epigenetic regulators essential for early development and function as critical transcriptional repressors. They include PRC1, PRC2, and PR-DUB, which control histone modifications such as H2AK119ub1 and H3K27me3. The nuclear distribution of these complexes and their associated ML364 modifications significantly influence gene transcription and 3D genome organization. Despite their importance, the mechanisms by which PcG complexes regulate 3D chromatin architecture remain poorly understood.
This study explores the role of PcG complexes in shaping 3D chromatin structure and compaction, examines how their dysregulation contributes to tumorigenesis, and considers the therapeutic potential of targeting these mechanisms.