The chromosome folding problem and how cells solve it

Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6424 - 6450

Published: Nov. 1, 2024

Every cell must solve the problem of how to fold its genome. We describe folded state chromosomes is result combined activity multiple conserved mechanisms. Homotypic affinity-driven interactions lead spatial partitioning active and inactive loci. Molecular motors through loop extrusion. Topological features such as supercoiling entanglements contribute chromosome folding dynamics, tethering loci sub-nuclear structures adds additional constraints. Dramatically diverse conformations observed throughout cycle across tree life can be explained differential regulation implementation these basic propose that first functions are mediate genome replication, compaction, segregation mechanisms have subsequently been co-opted for other roles, including long-range gene regulation, in different conditions, types, species.

Language: Английский

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Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100778 - 100778

Published: Feb. 1, 2025

Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target promoters. Whether distal enhancers require specific factors to orchestrate regulation remains unclear. Here, we used enhancer distance-controlled reporter screens find candidate factors. We depleted them and employed activity-by-contact predictions genome-wide classify genes based on distance. Predicted typically control tissue-restricted often are strong enhancers. cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range prioritizing over proximal HBB competing shared Long-range controlled sensitive perturbations of other regulatory proteins BET inhibitor JQ1, this being more a consequence their distinct features than Our work predicts that lengthening intervening sequences can help limit the expression specialized cells optimal trans-factor environments.

Language: Английский

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Genomic snowflakes: how the uniqueness of DNA folding allows us to smell the chemical universe

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102329 - 102329

Published: March 18, 2025

Language: Английский

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Cohesin positions the epigenetic reader Phf2 within the genome

The EMBO Journal, Journal Year: 2025, Volume and Issue: 44(3), P. 736 - 766

Published: Jan. 2, 2025

Language: Английский

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Solid phase transitions as a solution to the genome folding paradox

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Language: Английский

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Unfolding neural diversity: how dynamic three-dimensional genome architecture regulates brain function and disease

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: May 23, 2025

Abstract The advent of single cell multi-omic technologies has ushered in a revolution how we study the impact three-dimensional genome organization on brain cellular composition and function. Transcriptomic epigenomic studies reveal enormous diversity that is present mammalian nervous systems, raising question, “how does this arise for what its use?” Advances field nuclear architecture have illuminated our understanding folding gives rise to dynamic gene expression programs important healthy function disease. In review highlight recent work defining neuronal identity, maturation, plasticity are shaped by architecture. We discuss newly identified genetic variations influence contribute evolution species-unique behavioral functional traits. include examples both humans model organisms which maladaptive genomic causal agent Finally, make conclusions address future perspectives (4D nucelome) research.

Language: Английский

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Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 22, 2024

Abstract The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that is required for post-mitotic differentiation and function antigen-presenting dendritic cells (DCs), particularly antigen cross-presentation IL-12 secretion by type 1 conventional DCs (cDC1s) in vivo . organization was shaped DC-specifying transcription factor IRF8, which controlled looping chromosome compartmentalization, respectively. Notably, optimal expression IRF8 itself CTCF/cohesin-binding sites demarcating Irf8 gene. During DC activation, induction a subset genes with distal enhancers. Accordingly, deletion CTCF flanking Il12b gene reduced production cDC1s. Our data reveal an essential role cohesin-mediated regulation cell , its bi-directional crosstalk lineage-specifying factors.

Language: Английский

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Barcoding distinct neurons

Science, Journal Year: 2024, Volume and Issue: 385(6707), P. 370 - 371

Published: July 25, 2024

The genomic landscape of a cell surface protein reveals how neuron identity is displayed

Language: Английский

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Single-Cell Chromatin State Transitions During Epigenetic Memory Formation

Published: Jan. 1, 2024

Language: Английский

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