DNA supercoiling links transcription and chromatin architecture during human stem cell differentiation
Perez, C.; Murat, P.; Zeller, A.; Liu, K. C.; Crisp, A.; Sale, J. E.
Show abstract
Transcription imposes torsional stress on chromatin, leading to over- or under-winding of the DNA helix. Yet, how supercoiling evolves during dynamic changes in gene expression, and how it influences three-dimensional chromatin contacts in the densely packed human genome, remains unclear. Here, we map genome-wide negative supercoiling and chromatin interactions at high resolution in human embryonic stem cells, using the transcriptional changes that drive differentiation to explore their interplay at multiple scales. We demonstrate that gene activation increases negative supercoiling despite enhanced topoisomerase recruitment. Moreover, elevated negative supercoiling correlates with increased DNA contacts within domains at multiple scales, from genes to topologically associating domains, consistent with transcription-generated torsional stress enhancing contact frequency. Thus, negative supercoiling likely contributes to the genome architectural remodelling that accompanies the execution of developmental programs.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The chromatin remodeller CHD4 regulates transcription factor binding to both prevent activation of silent enhancers and maintain active regulatory elements 98%
- Oct4 primarily controls enhancer activity rather than accessibility 98%
- Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones 97%
Similar papers in this journal
Similar papers in this journal
- Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes 98%
- G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing 98%
- In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation 97%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.