Gene mobility elements mediate cell type specific genome organization and radial gene movement in vivo DOI Creative Commons
Tanguy Lucas, Lin-Ing Wang, Juniper Glass-Klaiber

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

ABSTRACT Understanding the level of genome organization that governs gene regulation remains a challenge despite advancements in chromatin profiling techniques. Cell type specific architectures may be obscured by averaging heterogeneous cell populations. Here we took reductionist perspective, starting with relocation hunchback to nuclear lamina Drosophila neuroblasts. We previously found this event terminates competence produce early-born neurons and is mediated an intronic 250 base-pair element, which term mobility element (GME). over 800 putative GMEs globally are accessible Polycomb (PcG) target sites. appear distinct from PcG response elements, however, largely inaccessible Performing situ Hi-C purified neuroblasts, form megabase-scale interactions, spanning multiple topologically associated domain borders, preferentially contacting other GMEs. These interactions stage-specific. Notably, undergo developmentally- timed mobilization to/from neuroblast lamina, swapping GFP reporter transgene intron GME relocates embryos. propose constitute organizational framework mediate gene-to-lamina during progenitor state transitions vivo .

Язык: Английский

Direct observation of a condensate effect on super-enhancer controlled gene bursting DOI Creative Commons
Manyu Du, Simon Hendrik Stitzinger, Jan-Hendrik Spille

и другие.

Cell, Год журнала: 2024, Номер 187(2), С. 331 - 344.e17

Опубликована: Янв. 1, 2024

Enhancers are distal DNA elements believed to loop and contact promoters control gene expression. Recently, we found diffraction-sized transcriptional condensates at genes controlled by clusters of enhancers (super-enhancers). However, a direct function endogenous in controlling expression remains elusive. Here, develop live-cell super-resolution multi-color 3D-imaging approaches investigate putative roles the regulation super-enhancer Sox2. In contrast enhancer distance, find instead that condensate's positional dynamics better predictor A basal bursting occurs when condensate is far (>1 μm), but burst size frequency enhanced moves proximity (<1 μm). Perturbations cohesin local do not prevent affect its enhancement. We propose three-way kissing model whereby interacts transiently with locus regulatory bursting.

Язык: Английский

Процитировано

71
Increased enhancer–promoter interactions during developmental enhancer activation in mammals DOI
Zhuoxin Chen, Valentina Snetkova, Grace Bower

и другие.

Nature Genetics, Год журнала: 2024, Номер 56(4), С. 675 - 685

Опубликована: Март 20, 2024

Язык: Английский

Процитировано

42
Epigenetic pioneering by SWI/SNF family remodelers DOI Creative Commons
Kami Ahmad, Sandipan Brahma, Steven Henikoff

и другие.

Molecular Cell, Год журнала: 2023, Номер 84(2), С. 194 - 201

Опубликована: Ноя. 27, 2023

In eukaryotic genomes, transcriptional machinery and nucleosomes compete for binding to DNA sequences; thus, a crucial aspect of gene regulatory element function is modulate chromatin accessibility transcription factor (TF) RNA polymerase binding. Recent structural studies have revealed multiple modes TF engagement with nucleosomes, but how initial "pioneering" results in steady-state further II (RNAPII) has been unclear. Even less well understood distant sites open interact one another, such as when developmental enhancers activate promoters release RNAPII productive elongation. Here, we review evidence the centrality conserved SWI/SNF family nucleosome remodeling complexes, both pioneering mediating enhancer-promoter contacts. Consideration unwrapping ATP hydrolysis activities together their architectural features, may reconcile occupancy rapid dynamics observed by live imaging.

Язык: Английский

Процитировано

29
The chromosome folding problem and how cells solve it DOI Creative Commons
Job Dekker, Leonid A. Mirny

Cell, Год журнала: 2024, Номер 187(23), С. 6424 - 6450

Опубликована: Ноя. 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.

Язык: Английский

Процитировано

11
Exploring the interplay between enhancer–promoter interactions and transcription DOI Creative Commons
Ryan Kittle, Michal Levo

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

Процитировано

2
Bridging spatial and temporal scales of developmental gene regulation DOI Creative Commons
Andrés Cardona, M. M. Peixoto,

Tohn Borjigin

и другие.

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 92, С. 102328 - 102328

Опубликована: Март 12, 2025

The development of multicellular organisms relies on the precise coordination molecular events across multiple spatial and temporal scales. Understanding how information flows from interactions to cellular processes tissue organization during is crucial for explaining remarkable reproducibility complex organisms. This review explores chromatin-encoded transduced localized transcriptional global gene expression patterns, highlighting challenge bridging these We discuss recent experimental findings theoretical frameworks, emphasizing polymer physics as a tool describing relationship between chromatin structure dynamics By integrating perspectives, we aim clarify regulation coordinated levels biological suggest strategies future approaches.

Язык: Английский

Процитировано

2
Super-enhancer interactomes from single cells link clustering and transcription DOI Creative Commons

Derek J. Le,

Antonina Hafner, Sadhana Gaddam

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 10, 2024

Summary Regulation of gene expression hinges on the interplay between enhancers and promoters, traditionally explored through pairwise analyses. Recent advancements in mapping genome folding, like GAM, SPRITE, multi-contact Hi-C, have uncovered multi-way interactions among super-enhancers (SEs), spanning megabases, yet not measured their frequency single cells or relationship clustering transcription. To close this gap, here we used multiplexed imaging to map 3D positions 376 SEs across thousands mammalian nuclei. Notably, our single-cell images reveal that while SE-SE contacts are rare, often form looser associations termed “communities”. These communities, averaging 4-5 SEs, assemble cooperatively under combined effects genomic tethers, Pol2 clustering, nuclear compartmentalization. Larger communities associated with more frequent larger transcriptional bursts. Our work provides insights about SE interactome challenge existing hypotheses context regulation.

Язык: Английский

Процитировано

7
The method in the madness: Transcriptional control from stochastic action at the single-molecule scale DOI Creative Commons

Peter H. Whitney,

Timothée Lionnet

Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102873 - 102873

Опубликована: Июль 1, 2024

Cell states result from the ordered activation of gene expression by transcription factors. Transcription factors face opposing design constraints: they need to be dynamic trigger rapid cell state transitions, but also stable enough maintain terminal identities indefinitely. Recent progress in live-cell single-molecule microscopy has helped define biophysical principles underlying this paradox. Beyond factor activity, experiments have revealed that at nearly every level regulation, control emerges multiple short-lived stochastic interactions, rather than deterministic, interactions typical other biochemical pathways. This architecture generates consistent outcomes can rapidly choreographed. Here, we highlight recent results demonstrate how order regulation apparent molecular-scale chaos and discuss remaining conceptual challenges.

Язык: Английский

Процитировано

4
Basic Epigenetic Mechanisms DOI
James Davie, Hedieh Sattarifard, S Sudhakar

и другие.

Sub-cellular biochemistry/Subcellular biochemistry, Год журнала: 2025, Номер unknown, С. 1 - 49

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression DOI Open Access
Yoshinori Kohwi, Xianrong Wong,

Mari Grange

и другие.

Опубликована: Март 13, 2025

Mammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another direct of base-unpairing regions (BURs), which genomic elements with high unwinding propensities. Published ChIP-seq datasets show highly accessible at enhancers CTCF sites, but not BURs. By employing urea ChIP-seq, retains only directly bound protein:DNA complexes, we found BURs, targets. SATB1-bound BUR interactions can cross multiple topologically associated domains (TADs) is required for these megabase-scale linked gene expression. BURs mainly within lamina (LADs) sequestered lamina, also in inter-LADs, binds a subset depending on type. Notably, despite mutually exclusive SATB1-binding profiles two methods, most peaks both real require SATB1. Together, propose has functionally distinct modes interaction form scaffold it indirectly tethers open chromatin. Such may provide gene-regulatory network underlying

Язык: Английский

Процитировано

0