Abstract
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 traced 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 from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter–enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.
Funder
European Research Council
European Union's Horizon 2020 research and innovation program
ATIP-Avenir
Agence Nationale de la Recherche
Investissements d'Avenir
Institut National de la Santé et de la Recherche Médicale
Canadian Institutes of Health Research
National Institutes of Health
Canada Foundation for Innovation
Ontario Ministry of Research and Innovation
Natural Sciences and Engineering Research Council of Canada
Oncode Institute
Dutch Cancer Society
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
16 articles.
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