Three‐dimensional genome structure and function DOI Creative Commons
Hao Liu,

Hsiangyu Tsai,

Maoquan Yang

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: July 8, 2023

Abstract Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, chromatin loop. These structures play crucial roles regulating gene expression, cell differentiation, disease progression. Deciphering the principles underlying 3D genome molecular mechanisms governing fate determination remains challenge. With advancements high‐throughput sequencing imaging techniques, hierarchical organization functional higher‐order have been gradually illuminated. This review systematically discussed hierarchy genome, effects cis‐regulatory elements interaction for spatiotemporally specific dynamic changes conformation during embryonic development, pathological diseases such as congenital developmental abnormalities cancer, which are attributed to alterations aberrations key proteins. Finally, prospects were made research about structure, function, genetic intervention, prevention, treatment, may offer some clues precise diagnosis treatment related diseases.

Language: Английский

Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells DOI Creative Commons
John Hunt, Christopher Samson, Alex du Rand

et al.

Human Genetics, Journal Year: 2023, Volume and Issue: 142(6), P. 705 - 720

Published: April 24, 2023

Abstract Genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) gene-editing system (CRISPR-Cas) is a valuable tool for fundamental applied research applications. Significant improvements in efficacy have advanced genome strategies into phase 3 human clinical trials. However, recent studies suggest that our understanding of outcomes has lagged behind developments made generating edits themselves. While many researchers analyzed on- off-target events through lens small insertions or deletions at predicted sites, screens larger structural variants (SVs) chromosomal abnormalities are not routinely performed. Full comprehensive validation effects required to ensure reproducibility accurately assess safety future Here we review SVs associated with CRISPR-editing cells origin highlight methods used detect avoid them.

Language: Английский

Citations

45
Computational methods for analysing multiscale 3D genome organization DOI
Yang Zhang, Lorenzo Boninsegna, Muyu Yang

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 123 - 141

Published: Sept. 6, 2023

Language: Английский

Citations

37
ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer DOI
Li‐Ping Ge, Xi Jin, Ding Ma

et al.

Cell Research, Journal Year: 2024, Volume and Issue: 34(1), P. 58 - 75

Published: Jan. 2, 2024

Language: Английский

Citations

12
Unveiling Alterations of Epigenetic Modifications and Chromatin Architecture Leading to Lipid Metabolic Reprogramming during the Evolutionary Trastuzumab Adaptation of HER2‐Positive Breast Cancer DOI Creative Commons
Ningjun Duan, Yijia Hua, Xueqi Yan

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 9, 2024

Abstract Secondary trastuzumab resistance represents an evolutionary adaptation of HER2‐positive breast cancer during anti‐HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their genetic epigenetic mechanisms. Here, transcriptome data is not only characterized also examined epigenomic 3D genome architecture information in both trastuzumab‐sensitive secondary‐resistant cells. The findings reveal that the global metabolic reprogramming may stem from genome‐wide alterations histone modifications chromatin structure. Specifically, transcriptional activities key genes involved lipid metabolism appear be regulated by variant promoter H3K27me3 H3K4me3 modifications, as well promoter‐enhancer interactions. These discoveries offer valuable insights into how cells adapt anti‐tumor drugs potential impact future diagnostic treatment strategies.

Language: Английский

Citations

12
Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification DOI
Zhao Ma, Mengting Li, Fuqiang Li

et al.

Gastric Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Language: Английский

Citations

1
G-Quadruplex Structures Are Key Modulators of Somatic Structural Variants in Cancers DOI Creative Commons
Rongxin Zhang, Huiling Shu, Yuqi Wang

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(8), P. 1234 - 1248

Published: Feb. 15, 2023

G-quadruplexes (G4) are noncanonical secondary genome structures. Aberrant formation of G4s can impair integrity. Investigation the relationship between and somatic structural variants (SV) in cancers could provide a better understanding role G4 cancer development progression. In this study, we combined bioinformatic approaches multiomics data to investigate connection SVs. Somatic SV breakpoints were significantly enriched regions, regardless subtypes. This enrichment was only observed regions demonstrated form cells ("active quadruplexes"), rather than with sequence compatible but without confirmed ("potential quadruplexes"). Several genomic features affected SVs, being notably strengthened at boundary topologically associated domains. also preferentially earlier replication timing open chromatin status. patients homologous recombination repair defects, substantially more strongly associated. Machine learning models constructed that showed propensity is potent feature for predicting density breakpoints. Altogether, these findings suggest structures play critical modulating production SVs cancers.G-quadruplex structure constitutes step cancers, suggesting G-quadruplex as potential targets future prevention treatment strategies.

Language: Английский

Citations

21
Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression DOI Creative Commons

Sara Pereira Cruz,

Qin Zhang, Raman Devarajan

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(11)

Published: Jan. 2, 2024

Abstract The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta‐analysis of multiple cohorts is performed which revealed that downregulation or genomic loss ITGA1 ITGA2 integrin genes associated with tumor progression worse prognosis. Genomic deletion both activated epithelial‐to‐mesenchymal transition (EMT) in benign epithelial cells, enhancing their invasive potential vitro converting them into tumorigenic cells vivo. Mechanistically, EMT induced by enhanced secretion autocrine activation TGFβ1 nuclear targeting YAP1. An unbiased genome‐wide co‐expression analysis large cohort datasets identified the transcription factor TEAD1 as key regulator expression while phenocopied dual α1‐ α2‐integrins Remarkably, clinical data aggressive together low synergistically impacted prognosis progression. This study thus demonstrated α2‐integrins, either via deletion/inactivation / locus , contributes to inducing TGFβ1‐driven EMT.

Language: Английский

Citations

6
When 3D genome changes cause disease: the impact of structural variations in congenital disease and cancer DOI Open Access
Joachim Weischenfeldt, Daniel M. Ibrahim

Current Opinion in Genetics & Development, Journal Year: 2023, Volume and Issue: 80, P. 102048 - 102048

Published: May 6, 2023

Language: Английский

Citations

10
Boosting the detection of enhancer-promoter loops via novel normalization methods for chromatin interaction data DOI Open Access
Xiaotao Wang,

Detong Shi,

Feiyang Xue

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Accurately detecting enhancer-promoter loops from genome-wide interaction data, such as Hi-C, is crucial for understanding gene regulation. Current normalization methods, Iterative Correction and Eigenvector decomposition (ICE), are commonly used to remove biases in Hi-C data prior chromatin loop detection. However, while structural or CTCF-associated signals retained, often greatly diminished after ICE similar making these regulatory harder detect. To address this limitation, we developed Raichu, a novel method normalizing contact data. Raichu identifies nearly twice many ICE, recovering almost all detected by revealing thousands of additional missed ICE. With its enhanced sensitivity loops, detects more biologically meaningful differential between conditions the same cell type. Furthermore, performs consistently across different sequencing depths platforms, including HiChIP, single-cell it versatile tool uncovering new insights into three- dimensional (3D) genomic organization transcriptional

Language: Английский

Citations

0
Chromatin hubs drive key regulatory networks in leukemia DOI
Alok Swaroop, Feng Yue

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(1), P. 1 - 2

Published: Jan. 1, 2025

Language: Английский

Citations

0