Structural variants drive context-dependent oncogene activation in cancer

Xu, Zhichao; Lee, Dong-Sung; Chandran, Sahaana; Le, Victoria T.; Bump, Rosalind; Yasis, Jean; Dallarda, Sofia; Marcotte, Samantha; Clock, Benjamin; Haghani, Nicholas; Cho, Chae Yun; Akdemir, Kadir C.; Tyndale, Sélène T.; Futreal, Andrew; McVicker, Graham; Wahl, Geoffrey M.; Dixon, Jesse R.

doi:10.1038/s41586-022-05504-4

Cited by 38 publications

(36 citation statements)

References 94 publications

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“… 289 Structural variation has been identified as a crucial mechanism underlying cancer development 262,263 . Genomic rearrangements can cause transcriptional dysregulation of proto‐oncogenes and oncogenes by altering interactions between cis‐regulatory elements in somatic cells, leading to abnormal proliferation and differentiation 264–266 …”

Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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

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Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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“…116 Algorithmic tools have been developed to identify SVs that may cause enhancer hijacking events. 117 These studies enrich current mechanistic studies on how chromatin structure is related to cancer development.…”

Section: Enhancer Hijacking: a Critical Phenomenon In Chromatin Aberr...mentioning

confidence: 81%

“…In several recent tumour‐related studies, it was discovered that enhancer hijacking events are the driving factors of high levels of oncogene expression 116 . Algorithmic tools have been developed to identify SVs that may cause enhancer hijacking events 117 . These studies enrich current mechanistic studies on how chromatin structure is related to cancer development.…”

Section: Chromatin Structure and Diseasesmentioning

confidence: 99%

3D genome perspective on cell fate determination, organ regeneration, and diseases

Zhong

Zhang

et al. 2023

Cell Proliferation

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The nucleosome is the fundamental subunit of chromatin. Nucleosome structures are formed by the combination of histone octamers and genomic DNA. Through a systematic and precise process of folding and compression, these structures form a 30‐nm chromatin fibre that is further organized within the nucleus in a hierarchical manner, known as the 3D genome. Understanding the intricacies of chromatin structure and the regulatory mode governing chromatin interactions is essential for unravelling the complexities of cellular architecture and function, particularly in relation to cell fate determination, regeneration, and the development of diseases. Here, we provide a general overview of the hierarchical structure of chromatin as well as of the evolution of chromatin conformation capture techniques. We also discuss the dynamic regulatory changes in higher‐order chromatin structure that occur during stem cell lineage differentiation and somatic cell reprogramming, potential regulatory insights at the chromatin level in organ regeneration, and aberrant chromatin regulation in diseases.

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“…The disruption of TAD boundaries can affect gene expression and is associated with various diseases and cancers. A recent study reported that the combination of genome profiling and CRISPR-Cas9 genome engineering could identify regions with repetitive changes in the 3D genome structure and predict oncogene activity (Xu et al, 2022). Nuclear lamina and constituent filament proteins, A/B type lamins, are located in the nuclear envelope.…”

Section: Chromatin Conformationmentioning

confidence: 99%

Epigenetic Regulations in Mammalian Cells: Roles and Profiling Techniques

Kim

Lee

2023

Molecules and Cells

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The genome is almost identical in all the cells of the body. However, the functions and morphologies of each cell are different, and the factors that determine them are the genes and proteins expressed in the cells. Over the past decades, studies on epigenetic information, such as DNA methylation, histone modifications, chromatin accessibility, and chromatin conformation have shown that these properties play a fundamental role in gene regulation. Furthermore, various diseases such as cancer have been found to be associated with epigenetic mechanisms. In this study, we summarized the biological properties of epigenetics and single-cell epigenomic profiling techniques, and discussed future challenges in the field of epigenetics.

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Structural variants drive context-dependent oncogene activation in cancer

Cited by 38 publications

References 94 publications

Three‐dimensional genome structure and function

Three‐dimensional genome structure and function

3D genome perspective on cell fate determination, organ regeneration, and diseases

Epigenetic Regulations in Mammalian Cells: Roles and Profiling Techniques

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