The spatial organization of transcriptional control

Nature Reviews Genetics, Год журнала: 2022, Номер 24(1), С. 53 - 68

Опубликована: Сен. 14, 2022

Язык: Английский

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Liquid–Liquid Phase Separation in Chromatin

Cold Spring Harbor Perspectives in Biology, Год журнала: 2021, Номер 14(2), С. a040683 - a040683

Опубликована: Июнь 14, 2021

Karsten Rippe Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, 69120 Heidelberg, Germany Correspondence: Karsten.Rippe{at}dkfz.de

Язык: Английский

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Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing

Nature Biotechnology, Год журнала: 2022, Номер 40(10), С. 1488 - 1499

Опубликована: Май 30, 2022

Язык: Английский

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Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 19, 2022

Abstract Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated cohesin CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale to what extent fine-scale regulatory interactions depend on extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, has enabled us generate the most detailed local interaction data date (20 bp resolution) precisely investigate effects of CTCF depletion architecture. Our reveal that cis -regulatory elements have distinct internal nano-scale structures, insulation dependent CTCF, but independent cohesin. In contrast, find causes a subtle reduction in longer-range enhancer-promoter can cause rewiring contacts. Together, our show not essential for interactions, contributes their robustness specificity precise regulation gene expression.

Язык: Английский

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The role of chromatin loop extrusion in antibody diversification

Nature reviews. Immunology, Год журнала: 2022, Номер 22(9), С. 550 - 566

Опубликована: Фев. 15, 2022

Язык: Английский

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Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness

Nature Genetics, Год журнала: 2023, Номер 55(2), С. 280 - 290

Опубликована: Янв. 30, 2023

Язык: Английский

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Chromatin accessibility: methods, mechanisms, and biological insights

Nucleus, Год журнала: 2022, Номер 13(1), С. 238 - 278

Опубликована: Ноя. 20, 2022

Access to DNA is a prerequisite the execution of essential cellular processes that include transcription, replication, chromosomal segregation, and repair. How proteins regulate these function in context chromatin its dynamic architectures an intensive field study. Over past decade, genome-wide assays new imaging approaches have enabled greater understanding how access genome regulated by nucleosomes associated proteins. Additional mechanisms may control accessibility vivo compaction phase separation – are beginning be understood. Here, we review ongoing development measurements, summarize different molecular structural shape landscape, detail many important biological functions linked accessibility.

Язык: Английский

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Loop stacking organizes genome folding from TADs to chromosomes

Molecular Cell, Год журнала: 2023, Номер 83(9), С. 1377 - 1392.e6

Опубликована: Май 1, 2023

Язык: Английский

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Direct observation of a condensate effect on super-enhancer controlled gene bursting

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

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The Mediator complex regulates enhancer-promoter interactions

Nature Structural & Molecular Biology, Год журнала: 2023, Номер 30(7), С. 991 - 1000

Опубликована: Июль 1, 2023

Abstract Enhancer-mediated gene activation generally requires physical proximity between enhancers and their target promoters. However, the molecular mechanisms by which interactions promoters are formed not well understood. Here, we investigate function of Mediator complex in regulation enhancer-promoter interactions, combining rapid protein depletion high-resolution MNase-based chromosome conformation capture approaches. We show that leads to reduced interaction frequencies, associated with a strong decrease expression. In addition, find increased CTCF-binding sites upon depletion. These changes chromatin architecture redistribution Cohesin on reduction occupancy at enhancers. Together, our results indicate complexes contribute provide insights into communication is regulated.

Язык: Английский

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