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健康与疾病中的三维基因组组织:癌症转化医学的新机遇

3D genome organization in health and disease: emerging opportunities in cancer translational medicine.

作者信息

Babu Deepak, Fullwood Melissa J

机构信息

a Cancer Science Institute of Singapore: Singapore; National University of Singapore ; Singapore.

b School of Biological Sciences; Nanyang Technological University ; Singapore.

出版信息

Nucleus. 2015;6(5):382-93. doi: 10.1080/19491034.2015.1106676.


DOI:10.1080/19491034.2015.1106676
PMID:26553406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4915485/
Abstract

Organizing the DNA to fit inside a spatially constrained nucleus is a challenging problem that has attracted the attention of scientists across all disciplines of science. Increasing evidence has demonstrated the importance of genome geometry in several cellular contexts that affect human health. Among several approaches, the application of sequencing technologies has substantially increased our understanding of this intricate organization, also known as chromatin interactions. These structures are involved in transcriptional control of gene expression by connecting distal regulatory elements with their target genes and regulating co-transcriptional splicing. In addition, chromatin interactions play pivotal roles in the organization of the genome, the formation of structural variants, recombination, DNA replication and cell division. Mutations in factors that regulate chromatin interactions lead to the development of pathological conditions, for example, cancer. In this review, we discuss key findings that have shed light on the importance of these structures in the context of cancers, and highlight the applicability of chromatin interactions as potential biomarkers in molecular medicine as well as therapeutic implications of chromatin interactions.

摘要

将DNA组织起来以适应空间受限的细胞核是一个具有挑战性的问题,吸引了所有科学学科的科学家的关注。越来越多的证据表明,基因组几何结构在影响人类健康的多种细胞环境中具有重要意义。在多种方法中,测序技术的应用极大地增进了我们对这种复杂组织(也称为染色质相互作用)的理解。这些结构通过将远端调控元件与其靶基因相连并调节共转录剪接,参与基因表达的转录调控。此外,染色质相互作用在基因组组织、结构变异形成、重组、DNA复制和细胞分裂中起关键作用。调节染色质相互作用的因子发生突变会导致病理状况的发展,例如癌症。在本综述中,我们讨论了揭示这些结构在癌症背景下重要性的关键发现,并强调了染色质相互作用作为分子医学潜在生物标志物的适用性以及染色质相互作用的治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/32b1fcd6dd76/kncl-06-05-1106676-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/3233445892dd/kncl-06-05-1106676-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/ca795772e9e9/kncl-06-05-1106676-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/f828831b3946/kncl-06-05-1106676-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/32b1fcd6dd76/kncl-06-05-1106676-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/3233445892dd/kncl-06-05-1106676-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/ca795772e9e9/kncl-06-05-1106676-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/f828831b3946/kncl-06-05-1106676-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/4915485/32b1fcd6dd76/kncl-06-05-1106676-g004.jpg

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3D genome organization in health and disease: emerging opportunities in cancer translational medicine.

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Brief Bioinform. 2025-5-1

[2]
A 3D Genome Atlas of Genetic Variants and Their Pathological Effects in Cancer.

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[3]
Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth.

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[4]
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Brief Bioinform. 2024-1-22

[5]
Biophysics is reshaping our perception of the epigenome: from DNA-level to high-throughput studies.

Biophys Rep (N Y). 2021-9-29

[6]
Haplotype-specific chromatin looping reveals genetic interactions of regulatory regions modulating gene expression in 8p23.1.

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[7]
Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells.

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[8]
Identification of mechanism of cancer-cell-specific reactivation of hTERT offers therapeutic opportunities for blocking telomerase specifically in human colorectal cancer.

Nucleic Acids Res. 2023-1-11

[9]
overexpression leads to increased chromatin interactions at super-enhancers and MYC binding sites.

Genome Res. 2022-4

[10]
Chromatin Conformation in Development and Disease.

Front Cell Dev Biol. 2021-8-4

本文引用的文献

[1]
Identification of Gene Positioning Factors Using High-Throughput Imaging Mapping.

Cell. 2015-8-13

[2]
Estrogen-induced chromatin decondensation and nuclear re-organization linked to regional epigenetic regulation in breast cancer.

Genome Biol. 2015-8-3

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Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.

Cell Rep. 2015-7-2

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Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.

Am J Hum Genet. 2015-7-2

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Proc Natl Acad Sci U S A. 2015-5-12

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Nat Commun. 2015-2-19

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Hum Mol Genet. 2015-5-1

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Cell. 2014-12-18

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A rare functional noncoding variant at the GWAS-implicated MIR137/MIR2682 locus might confer risk to schizophrenia and bipolar disorder.

Am J Hum Genet. 2014-11-26

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