RT Journal Article SR Electronic T1 Transcriptional regulation and chromatin architecture maintenance are decoupled modular functions at the Sox2 locus JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.02.09.479674 DO 10.1101/2022.02.09.479674 A1 Tiegh Taylor A1 Natalia Sikorska A1 Virlana M Shchuka A1 Sanjay Chahar A1 Chenfan Ji A1 Neil N Macpherson A1 Sakthi D Moorthy A1 Jennifer A Mitchell A1 Tom Sexton YR 2022 UL http://biorxiv.org/content/early/2022/02/10/2022.02.09.479674.abstract AB How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We trace nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream of the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, disruption of promoter-enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 expression. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.Competing Interest StatementThe authors have declared no competing interest.