Using a series of mouse mutants, we found that the Sox2 promoter does not require CTCF–cohesin loops to interact with distal enhancers. Surprisingly, mice with varying numbers of CTCF motifs in different positions showed that some distal enhancers can bypass boundaries that are created by CTCF–cohesin loops to ensure robust Sox2 expression.
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Huang, H. et al. CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains. Nat. Genet. 53, 1064–1074 (2021). This paper dissects the ability of CTCF loops to insulate Sox2 expression in embryonic stem cells.
Taylor, T. et al. Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus. Gene Dev. 36, 699–717 (2022). This paper describes CTCF-independent recruitment of enhancers of Sox2 in embryonic stem cells.
Kondoh H. & Lovell -Badge R. Sox2: Biology and Role in Development and Disease (Academic Press, 2015). A book with an extensive description of the multiple roles of SOX2 throughout development.
Brosch, R. et al. Synthetic regulatory genomics uncovers enhancer context dependence at the Sox2 locus. Preprint at https://doi.org/10.1101/2022.06.20.495832 (2022). A preprint study that reconstructs the enhancer SCR with different components.
Thompson, J. T. et al. Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages. Nat. Commun. 13, 4257 (2022). This paper describes how Sox2–SCR interaction frequencies correlate with the amount of H3K27ac (an epigenetic marker of enhancer activation) at SCR.
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This is a summary of: Chakraborty, S. et al. Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness. Nat. Genet. https://doi.org/10.1038/s41588-022-01295-6 (2023).
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Sox2 expression can be regulated across boundaries generated by CTCF–cohesin loops. Nat Genet 55, 174–175 (2023). https://doi.org/10.1038/s41588-022-01294-7