Block copolymer concepts of how transcription organizes the stem cell genome

Abstract

Stem cells display a highly dispersed genome organization that supports flexible gene regulation. Here, we present block copolymer concepts to explore how transcriptional activity from specific genomic regions, or ‘blocks’, shapes and controls several features of this architecture. Nascent transcripts tethered to chromatin can disrupt compaction and promote the formation of a micro-dispersed state of euchromatin, explaining one typical feature of the stem cell genome. A second feature is long-lived transcriptional clusters, which form via condensation at super-enhancer blocks and mediate both long-range interactions and local transcription factor accumulation. Lastly, we conceptualize promoters and gene bodies as a two-block polymer, for which sequential switching on and off of the polymer blocks controls the association and subsequent release of developmental genes with the long-lived clusters. The presented block copolymer framework provides explanations as well as hypotheses of how transcription-associated processes contribute to distinct features of stem cell genome organization.