Thread by @TomSexton_lab

Proud of this collaboration, getting to the bottom of the links between chromatin mobility, #transcription control and #loopextrusion processes, now on bioRxiv:
biorxiv.org/content/10.110…
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@mitchell_lab @tinekelenstra @EviSoutoglou @molina_lab @AkisPapantonis @kerstinbys

We tagged the Sox2 promoter and enhancer for their simultaneous tracking in live ES cells. While the two elements were frequently close , this distance remained largely unchanged on different means of inhibiting gene transcription.
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More importantly, we found that the promoter and enhancer were significantly less mobile than control regions. This was predicted by molecular dynamics simulations, taking loop extrusion and transcription factor-mediated clustering into account.
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Combined with MS2-labeling of Sox2 nascent transcripts, we found that the enhancer specifically becomes less mobile on transcriptional firing, whereas the gene is consistently constrained.
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This is consistent with the highly active Sox2 gene nucleating a transcriptional hub. Enhancer association with the hub, more than direct physical proximity to the gene, is linked to transcriptional firing.
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Deletion of CTCF sites causes local increased chromatin mobility, suggesting that stalled extrusion complexes, or their associated genomic architectures, constrains chromatin. Strikingly, deleting transcription factor binding sites at the enhancer had the OPPOSITE effect.
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Other results (see preprint for details!) suggest that loop extrusion and transcription are antagonistic processes. Transcription factor-mediated clustering brings elements together, just like CTCF sites, BUT also prevents loop extrusion processes from constraining chromatin.
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This has major implications for how these two important processes allow distal regulatory elements to “search” for their target genes. This work was possible with @ERC_Research funding and the amazing work of Angeliki, @cathie_erb, @dr_barbieri_mar and many more.
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