B14 Argyris Papantonis

The control and reorganization of 3D chromatin architecture is implicated in development and disease. However, the intricacies of the structure-to-function relationship of mammalian genomes remain poorly understood. We present experimental evidence that the highly abundant chromatin-binders HMGB1 and HMGB2 demarcate higher-order “loop” domains of the human genome and that their loss upon replicative arrest induces the striking spatial clustering of CTCF. Thus, we propose that HMGB1/B2 assume a central role in whole-genome architecture and lay out an experimental plan to dissect their roles in both proliferating and terminally-differentiated primary human cells under native conditions.