CRISPR technologies for precise epigenome editing

Nature Cell Biology, Год журнала: 2021, Номер 23(1), С. 11 - 22

Опубликована: Янв. 1, 2021

Язык: Английский

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Roles of transposable elements in the regulation of mammalian transcription

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(7), С. 481 - 497

Опубликована: Фев. 28, 2022

Язык: Английский

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The relationship between genome structure and function

Nature Reviews Genetics, Год журнала: 2020, Номер 22(3), С. 154 - 168

Опубликована: Ноя. 24, 2020

Язык: Английский

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On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

Journal of Biological Chemistry, Год журнала: 2020, Номер 295(13), С. 4134 - 4170

Опубликована: Фев. 15, 2020

Expansions of simple tandem repeats are responsible for almost 50 human diseases, the majority which severe, degenerative, and not currently treatable or preventable. In this review, we first describe molecular mechanisms repeat-induced toxicity, is connecting link between repeat expansions pathology. We then survey alternative DNA structures that formed by expandable review evidence formation these at core instability. Next, consequences presence long structure-forming level: somatic intergenerational instability, fragility, mutagenesis. discuss reasons gender bias in instability tissue specificity also known pathways replication, transcription, repair, chromatin state interact thereby promote possible persistence disease-causing genome. suggesting a payoff advantages having abundant simple-sequence eukaryotic genome function evolvability. Finally, two unresolved fundamental questions: (i) why does behavior differ model systems pedigrees, (ii) can use current knowledge on to cure expansion diseases?

Язык: Английский

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Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1

Nature Genetics, Год журнала: 2022, Номер 54(12), С. 1919 - 1932

Опубликована: Дек. 1, 2022

It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression most genes despite substantially perturbing three-dimensional (3D) genome folding at the level domains structural loops. To address this conundrum, we used high-resolution Micro-C nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to (3-h) CTCF, or WAPL. YY1 has been proposed as a regulator E-P loops, but also had minimal effects on transcription 3D folding. Strikingly, live-cell, single-molecule imaging revealed reduced factor (TF) binding chromatin. Thus, although cohesin, WAPL is not required for short-term maintenance gene expression, our results suggest may facilitate TFs search bind their targets more efficiently.

Язык: Английский

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Lamina-associated domains: peripheral matters and internal affairs

Genome biology, Год журнала: 2020, Номер 21(1)

Опубликована: Апрель 2, 2020

Abstract At the nuclear periphery, associations of chromatin with lamina through lamina-associated domains (LADs) aid functional organization genome. We review LADs and provide evidence LAD heterogeneity from cell ensemble single-cell data. are typically repressive environments in genome; nonetheless, we discuss findings lamin interactions regulatory elements active genes, role lamins may play genome regulation. address relationship between other organizers, involvement laminopathies. The current data lay basis for future studies on significance lamin-chromatin health disease.

Язык: Английский

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ecDNA hubs drive cooperative intermolecular oncogene expression

Nature, Год журнала: 2021, Номер 600(7890), С. 731 - 736

Опубликована: Ноя. 24, 2021

Язык: Английский

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Biomarkers of aging

Science China Life Sciences, Год журнала: 2023, Номер 66(5), С. 893 - 1066

Опубликована: Апрель 11, 2023

Язык: Английский

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In situ genome sequencing resolves DNA sequence and structure in intact biological samples

Science, Год журнала: 2021, Номер 371(6532)

Опубликована: Фев. 25, 2021

Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair resolution or direct localization. Here, we describe in situ sequencing (IGS), a method for simultaneously imaging genomes within intact biological samples. We applied IGS to human fibroblasts early mouse embryos, spatially localizing thousands genomic loci individual nuclei. Using these data, characterized parent-specific changes structure across embryonic stages, revealed single-cell chromatin domains zygotes, uncovered epigenetic memory global chromosome positioning embryos. These results demonstrate how can directly connect length scales from single pairs whole organisms.

Язык: Английский

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Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation

Genome biology, Год журнала: 2020, Номер 21(1)

Опубликована: Сен. 30, 2020

We present MUSTACHE, a new method for multi-scale detection of chromatin loops from Hi-C and Micro-C contact maps. MUSTACHE employs scale-space theory, technical advance in computer vision, to detect blob-shaped objects is scalable kilobase-resolution maps reports that are highly consistent between replicates datasets. Compared other loop callers, such as HiCCUPS SIP, recovers higher number published ChIA-PET HiChIP well linking promoters regulatory elements. Overall, enables an efficient comprehensive analysis loops. Available at: https://github.com/ay-lab/mustache .

Язык: Английский

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