Genome biology · 2025
Regulatory roles of three-dimensional structures of chromatin domains.
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Li Kelly Yichen, Cao Qin, Chow Savio Ho-Chit, Nicoletti Chiara, Puri Pier Lorenzo, Wang Huating, Leung Danny, Yip Kevin Y
Аннотация
BACKGROUND: Transcriptional enhancers usually, but not always, regulate genes within the same topologically associating domain (TAD). We hypothesize that this incomplete insulation is partially 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.
RESULTS: Here we show that a simple measure, the intra-TAD ratio, can quantify the coreness of a region with respect to the single-cell domains to which it belongs. We show that domain surfaces are permissive for high gene expression. Cell type-specific active cis-regulatory elements, active histone marks, and transcription factor binding sites are enriched on domain surfaces, most strongly in chromatin subcompartments typically considered inactive.
CONCLUSIONS: These findings suggest a model of gene regulation that involves positioning active cis-regulatory elements on domain surfaces. We also find that disease-associated non-coding variants are enriched on domain surfaces.
RESULTS: Here we show that a simple measure, the intra-TAD ratio, can quantify the coreness of a region with respect to the single-cell domains to which it belongs. We show that domain surfaces are permissive for high gene expression. Cell type-specific active cis-regulatory elements, active histone marks, and transcription factor binding sites are enriched on domain surfaces, most strongly in chromatin subcompartments typically considered inactive.
CONCLUSIONS: These findings suggest a model of gene regulation that involves positioning active cis-regulatory elements on domain surfaces. We also find that disease-associated non-coding variants are enriched on domain surfaces.