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bioRxiv · 10.1101/2022.07.22.501196

Regulatory roles of three-dimensional structures of topologically associating domains

Li, K. Y.·Cao, Q.·Wang, H.·Leung, D. C. Y.·Yip, K. Y.
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Abstract

1Transcriptional enhancers usually, but not always, regulate genes within the same topologically associating domain (TAD). We hypothesize that this incomplete insulation is due to three-dimensional structures of corresponding chromatin domains in individual cells: Whereas enhancers and genes buried inside the "core" of a domain interact mostly with other regions in the same domain, those on the "surface" can more easily interact with the outside. Here we show that a simple measure, the intra-TAD ratio, can quantify the "coreness" of a region with respect to single-cell domains it belongs. We show that domain surfaces are permissive for high gene expression, and cell type-specific active cis-regulatory elements (CREs), active histone marks, and transcription factor binding sites are enriched on domain surfaces, most strongly in chromatin subcompartments typically considered inactive. These findings suggest a "domain surface CRE" model of gene regulation. We also find that disease-associated non-coding variants are enriched on domain surfaces.

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Li, K. Y., Cao, Q., Wang, H., Leung, D. C. Y., Yip, K. Y.. 2022-07-23. Regulatory roles of three-dimensional structures of topologically associating domains. https://doi.org/10.1101/2022.07.22.501196

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