Deciphering Multi-way Interactions in the Human Genome

Lindsly, Stephen; Chen, Can; Dilworth, Sam; Jeyarajan, Sivakumar; Meixner, Walter; Stansbury, Cooper; Cicalo, Anthony; Beckloff, Nicholas; Ryan, Charles W.; Surana, Amit; Wicha, Max S.; Omenn, Gilbert S.; Muir, Lindsey A.; Rajapakse, Indika

doi:10.1101/2021.08.15.456363

Cited by 2 publications

(2 citation statements)

References 79 publications

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“…Similarly, distinct ER α , KLF1, and NF κ B factories specialize in transcribing genes involved in the estrogen response, globin production, and inflammation [16–18]. One important consequence of this organisation is the creation of 3D networks, in which genes sharing the same TFs are cotranscribed in the same clusters, and so give contacts detected by techniques like Hi-C (a high-throughput variant of chromosome conformation capture), genome architecture mapping, and pore-C [2, 19–21].…”

Section: Introductionmentioning

confidence: 99%

Cluster size determines morphology of transcription factories in human cells

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Suma

et al. 2023

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Within each human cell, different kinds of RNA polymerases and a panoply of transcription factors bind chromatin to simultaneously determine 3D chromosome structure and transcriptional programme. Experiments show that, in some cases, different proteins segregate to form specialised transcription factories; in others they mix together, binding promiscuously the same chromatin stretch. Here, we use Brownian dynamics simulations to study a polymer model for chromosomes accounting for multiple types ('colours') of chromatin-binding proteins. Our multi-colour model shows the spontaneous emergence of both segregated and mixed clusters of chromatin bound proteins, depending mainly on their size, thereby reconciling the previous experimental observations. Additionally, remarkable small-world networks emerge; in these, positive and negative correlations in activities of transcription units provide simple explanations of why adjacent units in large domains are co-transcribed so often, and how one eQTL (expression quantitative trait locus) can up-regulate some genes and down-regulate others. We also explain how local genome edits induce distant om- nigenic and pangenomic effects, and develop ways to predict activities of all transcription units on human chromosomes. All results point to 1D location being a key determinant of transcription, consistently with the conservation of synteny seen between rapidly-evolving enhancers and their more stable target genes.

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Section: Introductionmentioning

confidence: 99%

Cluster size determines morphology of transcription factories in human cells

Semeraro

Negro

Suma

et al. 2023

Preprint

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“…To fill this gap, we developed the Multi-Nucleic Acid Interaction Mapping in Single Cell (MUSIC) technique, which enables the simultaneous profiling of gene expression and co-complexed DNA sequences with or without co-complexed RNA at the single-cell level. The architecture of chromatin can encompass both pairwise and multiplex chromatin interactions, highlighting the intricate nature of chromatin complexes 9,[24][25][26][27] . ChIA-Drop technology has facilitated the mapping of multiplex chromatin interactions at single-complex resolution from bulk cells, revealing that multiplex chromatin interactions are prevalent in Drosophila 24 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell multiplex chromatin and RNA interactions in aging human brain

Luo

Wen

Zhao

et al. 2023

Preprint

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The dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA. Here, we introduce the Multi-Nucleic Acid Interaction Mapping in Single Cell (MUSIC) technique to enable simultaneous profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within a single nucleus. We applied MUSIC to profile >9,000 single nuclei in the human frontal cortex. MUSIC-derived single-nucleus transcriptomes provide a comprehensive categorization of cortical cell types, subtypes and cellular states. The genomic sequences of highly-expressed genes frequently co-complex with their flanking genomic regions, forming what we refer to as Gene-Expression-Associated Stripes (GEAS), which exemplify the intricate coordination between transcription and chromatin architecture at the single-cell level. Additionally, we observed significant heterogeneity among female cortical cells in the association between the XIST long non-coding RNA (lncRNA) and the X chromosome (XIST-chrX association, quantified as XAL). Cells with high XAL demonstrated a greater difference in spatial organization between the XIST-associated (Xi) and non-associated (Xa) X chromosomes compared to XAL-low cells. Notably, excitatory neurons displayed enrichment in XAL-high cells and exhibited a more pronounced disparity in spatial organization between Xi and Xa compared to other cell types. The MUSIC technique offers a powerful tool for future investigations into chromatin architecture and transcription at a cellular resolution within complex tissues.

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Deciphering Multi-way Interactions in the Human Genome

Cited by 2 publications

References 79 publications

Cluster size determines morphology of transcription factories in human cells

Cluster size determines morphology of transcription factories in human cells

Single-cell multiplex chromatin and RNA interactions in aging human brain

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