Super-enhancers in transcriptional regulation and genome organization DOI Creative Commons
Xi Wang, Murray J. Cairns, Jian Yan

et al.

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: unknown

Published: Oct. 22, 2019

Gene expression is precisely controlled in a stage and cell-type-specific manner, largely through the interaction between cis-regulatory elements their associated trans-acting factors. Where these components aggregate promoters enhancers, they are able to cooperate modulate chromatin structure support engagement long-range 3D superstructures that shape dynamics of cell's genomic architecture. Recently, term 'super-enhancer' has been introduced describe hyper-active regulatory domain comprising complex array sequence work together control key gene networks involved cell identity. Here, we survey unique characteristics super-enhancers compared other enhancer types summarize recent advances our understanding biological role regulation. In particular, discuss capacity attract formation phase-separated condensates, generate three-dimensional genome structures activate target genes. We also propose multi-stage transition model explain evolutionary pressure driving development organisms, highlight potential for involvement tumorigenesis. Finally, more broadly human health disorders related therapeutic interventions.

Language: Английский

CRISPR technologies for precise epigenome editing DOI
Muneaki Nakamura, Yuchen Gao, Antonia A. Dominguez

et al.

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 11 - 22

Published: Jan. 1, 2021

Language: Английский

Citations

357
Roles of transposable elements in the regulation of mammalian transcription DOI
Raquel Fueyo, Julius Judd, Cédric Feschotte

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(7), P. 481 - 497

Published: Feb. 28, 2022

Language: Английский

Citations

268
On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability DOI Creative Commons
Alexandra N. Khristich, Sergei M. Mirkin

Journal of Biological Chemistry, Journal Year: 2020, Volume and Issue: 295(13), P. 4134 - 4170

Published: Feb. 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?

Language: Английский

Citations

253
The relationship between genome structure and function DOI
A. Marieke Oudelaar, Douglas R. Higgs

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(3), P. 154 - 168

Published: Nov. 24, 2020

Language: Английский

Citations

253
Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1 DOI Creative Commons
Tsung-Han S. Hsieh, Claudia Cattoglio, Elena Slobodyanyuk

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1919 - 1932

Published: Dec. 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.

Language: Английский

Citations

251
Lamina-associated domains: peripheral matters and internal affairs DOI Creative Commons
Nolwenn Briand, Philippe Collas

Genome biology, Journal Year: 2020, Volume and Issue: 21(1)

Published: April 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.

Language: Английский

Citations

219
ecDNA hubs drive cooperative intermolecular oncogene expression DOI
King L. Hung, Kathryn E. Yost, Liangqi Xie

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7890), P. 731 - 736

Published: Nov. 24, 2021

Language: Английский

Citations

214
Biomarkers of aging DOI Open Access

Hainan Bao,

Jiani Cao, Mengting Chen

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Citations

213
In situ genome sequencing resolves DNA sequence and structure in intact biological samples DOI Open Access

Andrew C. Payne,

Zachary Chiang, Paul Reginato

et al.

Science, Journal Year: 2021, Volume and Issue: 371(6532)

Published: Feb. 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.

Language: Английский

Citations

185
Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation DOI Creative Commons

Abbas Roayaei Ardakany,

Halil Tuvan Gezer,

Stefano Lonardi

et al.

Genome biology, Journal Year: 2020, Volume and Issue: 21(1)

Published: Sept. 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 .

Language: Английский

Citations

165