SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks

Nature Methods, Год журнала: 2023, Номер 20(9), С. 1355 - 1367

Опубликована: Июль 13, 2023

Abstract Joint profiling of chromatin accessibility and gene expression in individual cells provides an opportunity to decipher enhancer-driven regulatory networks (GRNs). Here we present a method for the inference GRNs, called SCENIC+. SCENIC+ predicts genomic enhancers along with candidate upstream transcription factors (TFs) links these target genes. To improve both recall precision TF identification, curated clustered motif collection more than 30,000 motifs. We benchmarked on diverse datasets from different species, including human peripheral blood mononuclear cells, ENCODE cell lines, melanoma states Drosophila retinal development. Next, exploit predictions study conserved TFs, GRNs between mouse types cerebral cortex. Finally, use dynamics regulation differentiation trajectories effect perturbations state. is available at scenicplus.readthedocs.io .

Язык: Английский

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Deciphering the multi-scale, quantitative cis-regulatory code

Molecular Cell, Год журнала: 2023, Номер 83(3), С. 373 - 392

Опубликована: Янв. 23, 2023

Uncovering the cis-regulatory code that governs when and how much each gene is transcribed in a given genome cellular state remains central goal of biology. Here, we discuss major layers regulation influence transcriptional outputs are encoded by DNA sequence context. We first transcription factors bind specific sequences dosage-dependent cooperative manner then proceed to cofactors facilitate factor function mediate activity modular elements such as enhancers, silencers, promoters. consider complex poorly understood interplay these diverse within regulatory landscapes its relationships with chromatin states nuclear organization. propose mechanistically informed, quantitative model integrates multiple will be key ultimately cracking code.

Язык: Английский

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Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq

Science, Год журнала: 2023, Номер 380(6649), С. 1070 - 1076

Опубликована: Июнь 8, 2023

Much progress has been made recently in single-cell chromosome conformation capture technologies. However, a method that allows simultaneous profiling of chromatin architecture and gene expression not reported. Here, we developed an assay named "Hi-C RNA-seq employed simultaneously" (HiRES) performed it on thousands single cells from developing mouse embryos. Single-cell three-dimensional genome structures, despite being heavily determined by the cell cycle developmental stages, gradually diverged type-specific manner as development progressed. By comparing pseudotemporal dynamics interactions with expression, found widespread rewiring occurred before transcription activation. Our results demonstrate establishment specific is tightly related to transcriptional control functions during lineage specification.

Язык: Английский

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Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project

Molecular Cell, Год журнала: 2023, Номер 83(15), С. 2624 - 2640

Опубликована: Июль 6, 2023

Язык: Английский

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TADs: Dynamic structures to create stable regulatory functions

Current Opinion in Structural Biology, Год журнала: 2023, Номер 81, С. 102622 - 102622

Опубликована: Июнь 9, 2023

Язык: Английский

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Real-time single-molecule imaging of transcriptional regulatory networks in living cells

Nature Reviews Genetics, Год журнала: 2024, Номер 25(4), С. 272 - 285

Опубликована: Янв. 9, 2024

Язык: Английский

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Resolving the three-dimensional interactome of human accelerated regions during human and chimpanzee neurodevelopment

Cell, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Exploring the interplay between enhancer–promoter interactions and transcription

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 90, С. 102303 - 102303

Опубликована: Янв. 14, 2025

Enhancers in metazoan genomes are known to activate their target genes across both short and long genomic distances. Recent advances chromosome conformation capture assays single-cell imaging have shed light on the underlying chromatin contacts dynamics. Yet relationship between 3D physical enhancer-promoter (E-P) interactions transcriptional activation remains unresolved. In this brief review, we discuss recent studies exploring scales: from developmental stages minutes surrounding tissue level single-allele subcellular We how seemingly contradictory observations might be reconciled contribute a refined causal E-P transcription, with mutual influences.

Язык: Английский

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Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 12, 2023

Topologically Associating Domains (TADs) separate vertebrate genomes into insulated regulatory neighborhoods that focus genome-associated processes. TADs are formed by Cohesin-mediated loop extrusion, with many TAD boundaries consisting of clustered binding sites the CTCF insulator protein. Here we determine how this clustering contributes to blocking extrusion and insulation between TADs. We identify enrichment three features at strong boundaries, strongly bound closely spaced peaks, a further DNA-binding motifs within these peaks. Using multi-contact Nano-C analysis in cells normal perturbed binding, establish individual contribute but an incomplete manner. When clustered, thus create stepwise neighboring Based on results, propose model whereby multiple instances temporal

Язык: Английский

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Size limits the sensitivity of kinetic schemes

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 8, 2023

Abstract Living things benefit from exquisite molecular sensitivity in many of their key processes, including DNA replication, transcription and translation, chemical sensing, morphogenesis. At thermodynamic equilibrium, the basic biophysical mechanism for is cooperative binding, which it can be shown that Hill coefficient, a measure, cannot exceed number binding sites. Generalizing this fact, we find any kinetic scheme, at or away very simple structural quantity, size support perturbation, always limits effective coefficient. We show how bound sheds light on unifies diverse mechanisms, proofreading nonequilibrium Monod-Wyman-Changeux (MWC) model proposed E. coli flagellar motor switch, representing each case simple, precise bridge between experimental observations models write down. In pursuit mechanisms saturate bound, mechanism, nested hysteresis, with exponential sites, implications our understanding gene regulation function biomolecular condensates.

Язык: Английский

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