Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(7), С. 574 - 591

Опубликована: Фев. 27, 2024

Язык: Английский

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Ultra-long-range interactions between active regulatory elements

Genome Research, Год журнала: 2023, Номер 33(8), С. 1269 - 1283

Опубликована: Июль 14, 2023

Contacts between enhancers and promoters are thought to relate their ability activate transcription. Investigating factors that contribute such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies millions of pairs

Язык: Английский

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Epigenetics in Neurodegenerative Diseases

Sub-cellular biochemistry/Subcellular biochemistry, Год журнала: 2025, Номер unknown, С. 73 - 109

Опубликована: Янв. 1, 2025

Язык: Английский

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Hypoxia-induced CTCF mediates alternative splicing via coupling chromatin looping and RNA Pol II pause to promote EMT in breast cancer

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115267 - 115267

Опубликована: Фев. 1, 2025

Hypoxia influences the epithelial-mesenchymal transition (EMT) through remodeling of chromatin structure, epigenetics, and alternative splicing. drives CCCTC-binding factor (CTCF) induction hypoxia-inducible 1-alpha (HIF1α), which promotes EMT, although underlying mechanisms remain unclear. We find that hypoxia significantly increases CTCF occupancy at various EMT-related genes. present a CTCF-mediated intricate mechanism promoting EMT wherein binding collagen type V alpha 1 chain (COL5A1) promoter is crucial for COL5A1 upregulation under hypoxia. Additionally, exon64A inclusion in mutually exclusive splicing event COL5A1exon64 (exon64A/64B). Notably, mediates promoter-alternatively spliced exon upstream looping regulates DNA demethylation distal exon64A. This further RNA polymerase II pause COL5A1exon64A, leading to its Genome-wide study indicates association gained with many cancer-related genes, similar proposed model. Specifically, disrupting HIF1α-CTCF-COL5A1exon64A axis dCas9-DNMT3A system alleviates hypoxic cancer cells may represent novel therapeutic target breast cancer.

Язык: Английский

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Cell type- and transcription-independent spatial proximity between enhancers and promoters

Molecular Biology of the Cell, Год журнала: 2024, Номер 35(7)

Опубликована: Май 8, 2024

Cell type-specific enhancers are critically important for lineage specification. The mechanisms that determine cell-type specificity of enhancer activity, however, not fully understood. Most current models how function invoke physical proximity between elements and their target genes. Here, we use an imaging-based approach to examine the spatial relationship cell genes with single-cell resolution. Using high-throughput microscopy, measure distance from promoters active inactive in individual pancreatic cells derived distinct lineages. We find increased all promoter-enhancer pairs relative non-enhancer separated by similar genomic distances. Strikingly, was unrelated tissue-specific activity. Furthermore, did correlate expression status Our results suggest exist a distinctive chromatin environment but genome folding is universal driver function.

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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Liquid condensates: a new barrier to loop extrusion?

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Фев. 20, 2025

Liquid–liquid phase separation (LLPS), driven by dynamic, low-affinity multivalent interactions of proteins and RNA, results in the formation macromolecular condensates on chromatin. These structures are likely to provide high local concentrations effector factors responsible for various processes including transcriptional regulation DNA repair. In particular, enhancers, super-enhancers, promoters serve as platforms condensate assembly. current paradigm, enhancer-promoter (EP) interaction could be interpreted a result enhancer- promoter-based contact/fusion. There is increasing evidence that spatial juxtaposition enhancers provided loop extrusion (LE) SMC complexes. Here, we propose may act barriers LE, thereby contributing nuclear contacts between regulatory genomic elements.

Язык: Английский

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Molecular mechanisms altering cell identity in cancer

Oncogene, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Язык: Английский

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The spatial choreography of mRNA biosynthesis

Journal of Cell Science, Год журнала: 2025, Номер 138(4)

Опубликована: Фев. 15, 2025

ABSTRACT Properly timed gene expression is essential for all aspects of organismal physiology. Despite significant progress, our understanding the complex mechanisms governing dynamics regulation in response to internal and external signals remains incomplete. Over past decade, advances technologies like light cryo-electron microscopy (Cryo-EM), tomography (Cryo-ET) high-throughput sequencing have spurred new insights into traditional paradigms expression. In this Review, we delve recent concepts addressing ‘where’ ‘when’ transcription RNA splicing occur within cells, emphasizing dynamic spatial temporal organization cell nucleus.

Язык: Английский

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Redefining enhancer action: Insights from structural, genomic, and single-molecule perspectives

Current Opinion in Cell Biology, Год журнала: 2025, Номер 95, С. 102527 - 102527

Опубликована: Май 16, 2025

This review explores recent emerging insights into enhancer action, focusing on underexplored aspects such as the physical size of regulatory elements, stochasticity transcription factor binding and chromatin structure, role nonlinear processes in reconciling longstanding discrepancies between theoretical models experimental observations. Together, these provide a nuanced view biology, highlighting complexity gene regulation need for innovative methodologies to further decode mechanisms.

Язык: Английский

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