The DOI matches its Crossref record; 71 of the 73 references it cites were found in a registry or an index.
Activation of proto-oncogenes by disruption of chromosome neighborhoods
Open accessAbstract
The spread of bad neighborhoods: Our genomes have complex three-dimensional (3D) arrangements that partition and regulate gene expression. Cancer cells frequently have their genomes grossly rearranged, disturbing this intricate 3D organization. Hnisz et al. show that the disruption of these 3D neighborhoods can bring oncogenes under the control of regulatory elements normally kept separate from them (see the Perspective by Wala and Beroukim). These novel juxtapositions can result in the inappropriate activation of oncogenes. Science , this issue p. 1454 ; see also p. 1398
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In the citing paper
“While genetic perturbation of CTCF binding has been shown to result in misregulation of gene expression in various cell lines and cancer9–11,28”
From Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo (2017) · cites this paper as [10]
In the citing paper
“Boundary disruption has recently been linked to cancer and diseases of limb development (Flavahan et al., 2016; Hnisz et al., 2016; Lupianez et al., 2015)”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Hnisz et al., 2016
In the citing paper
“Recent high-resolution Chromosome-Conformation-Capture sequencing studies have revealed that TAD boundaries are perturbed in rare human limb malformation diseases (Lupianez et al., 2015) and certain types of cancers (Flavahan et al., 2016; Hnisz et al., 2016), leading to enhancer miswiring and pathogenic disruption of gene expression.”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Hnisz et al., 2016
In the citing paper
“Several other studies have reported the deregulation of chromatin folding structures in different cancer types11,15,16.”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [15]
In the citing paper
“In a dozen loci and in multiple cell types, CRISPR/Cas9 deletion of CTCF binding sites at the anchors of insulated neighborhoods have been shown to produce changes in the expression of genes within the neighborhoods and immediately adjacent to the deleted neighborhood boundary.”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“Somatic mutations occur frequently and recurrently in the loop anchors of oncogene-containing Insulated neighborhoods in a variety of cancer cells (Figure 2E).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“Similarly, in T cell leukemia cells, ~90% of all enhancer or promoter-related DNA loops occur within insulated neighborhood boundaries (Hnisz et al., 2016).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“Silent proto-oncogenes typically occur within insulated neighborhoods and genetic modification of the neighborhood loop anchors can cause activation of these oncogenes (Flavahan et al., 2016; Hnisz et al., 2016).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“The vast majority of enhancer-gene interactions occur within insulated neighborhoods (Dowen et al., 2014; Hnisz et al., 2016; Ji et al., 2016; Phillips-Cremins et al., 2013).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“These observations are consistent with the idea that mutations that alter the loop anchor sites of oncogene-containing insulated neighborhoods make an important contribution to the misregulation of gene expression that is inherent to the cancer state (Flavahan et al., 2016; Hnisz et al., 2016; Katainen et al., 2015).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“Furthermore, chromosomal rearrangements such as translocations or deletions which activate oncogenes also disrupt insulated neighborhoods around those genes without altering the sequence of the gene itself (Groschel et al., 2014; Hnisz et al., 2016).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
In the citing paper
“Studies on insulated neighborhoods have estimated that approximately 80% of neighborhood boundaries of shared by any two cell types (Hnisz et al., 2016; Ji et al., 2016).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Hnisz et al., 2016
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Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · cited 1×
“This method yielded similar number of interactions as the correction of p-values by the Benjamini-Hochberg procedure (33) to control for multiple hypothesis testing.”
MethodUltrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · cited 2×
“1 (bowtie -e 70 -k 1 -m 1 -v 2 -p 4 --best --strata –S) (28).”
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · cited 4×
“CTCFChIP-seq and cohesin ChIA-PET interactions in Jurkat (T-ALL), GM12878 (lymphoblastoid), and K562 (CML) cells are displayed.”
BackgroundInfluentialMapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696 · cited 1×
“For a gene to be considered expressed the cutoff of >1 RPKM was used (50).”
MethodTopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212 · cited 4×
“Comparison of the Jurkat T-ALL ChIA-PET interactions to interactions described in other cell types Interactions detected using Hi-C data in GM12878, HeLa, HMEC, HUVEC, IMR90, K562, KBM7 and NHEK were downloaded from a previous study (36).”
BackgroundMethodInfluentialComprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898
Self-citationVogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · cited 1×
“1A), and identifying such mutations in patient genomes is a major goal of cancer genomics (2, 3).”
BackgroundTopological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · cited 2×
“The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia.”
BackgroundA Direct Approach to False Discovery Rates
Storey, J. D. (2002) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/1467-9868.00346 · Cited by 5,603 · cited 1×
“To correct for multiple hypothesis testing, we converted all the p-values into q-values via pFDR (68) using the Bioconductor qvalue package.”
Method
Flagged first, then by citations
2 of the 73 references couldn’t be matched to a known paper.
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Items 301–400 of 999
cLoops2: a full-stack comprehensive analytical tool for chromatin interactions
Cao, Y., Liu, S., Ren, G., Tang, Q., & Zhao, K. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1233 · Cited by 41
Dissection of a CTCF topological boundary uncovers principles of enhancer-oncogene regulation
Kim, K. L., Rahme, G. J., Goel, V. Y., Farran, C. A. E., Hansen, A. S., & Bernstein, B. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.02.007 · Cited by 42
The impact of HTLV-1 on the cellular genome
Cook, L. B. M., Melamed, A., Yaguchi, H., & Bangham, C. R. M. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.07.013 · Cited by 40
Regulation of Latency in the Human T Cell Leukemia Virus, HTLV-1
Bangham, C. R. M., Miura, M., Kulkarni, A., & Matsuoka, M. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015501 · Cited by 45
Analysis of the structural variability of topologically associated domains as revealed by Hi-C
Sauerwald, N., Singhal, A., & Kingsford, C. (2019) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqz008 · Cited by 38
“and disabilities, including many cancers [26, 28, 18, 19], deformation or malformation of limbs during development [25], and severe brain anomalies [41], but we do not have a sense of the expected variation of TADs genome-wide.”
LATS kinase–mediated CTCF phosphorylation and selective loss of genomic binding
Luo, H., Yu, Q., Liu, Y., Tang, M., Liang, M., Zhang, D., Xiao, T. S., Wu, L., Tan, M., Ruan, Y., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaw4651 · Cited by 39
Hilliard, W., & Lee, K. H. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27599 · Cited by 41
CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction
Galan, S., Machnik, N., Kruse, K., Díaz, N., Martı́-Renom, M. A., & Vaquerizas, J. M. (2020) · Nature Genetics · doi:10.1038/s41588-020-00712-y · Cited by 38
Rheinbay, E., Nielsen, M. M., Abascal, F., Tiao, G., Hornshøj, H., Hess, J. M., Pedersen, R. I., Feuerbach, L., Sabarinathan, R., Madsen, T. L., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/237313 · Cited by 40
The FOXO family of transcription factors: key molecular players in gastric cancer
Liu, Y., Ao, X., Jia, Y., Li, X., Wang, Y., & Wang, J. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02219-x · Cited by 39
“Aberrant chromatin structures are found to play a positive role in GC progression by altering gene expression [6].”
BackgroundFrom Genotype to Phenotype: Through Chromatin
Romanowska, J., & Joshi, A. (2019) · Genes · doi:10.3390/genes10020076 · Cited by 39
León, T. E., Rapoz-D’Silva, T., Bertoli, C., Rahman, S., Magnussen, M., Philip, B., Farah, N., Richardson, S. E., Ahrabi, S., Guerra‐Assunção, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0789 · Cited by 39
“The cohesin (SMC1) ChIA-PET interactions from Hnisz et al., 2016 are displayed above the ChIP-seq profiles (intensity of pink arc represents interaction score).”
BackgroundTranscriptional dysregulation by aberrant enhancer activation and rewiring in cancer
Okabe, A., & Kaneda, A. (2021) · Cancer Science · doi:10.1111/cas.14884 · Cited by 41
Chromosome compartmentalization alterations in prostate cancer cell lines model disease progression
Martin, R. S., Das, P., Marques, R. D. R., Xu, Y., Roberts, J. M., Sanders, J. T., Golloshi, R., & McCord, R. P. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202104108 · Cited by 40
“With the advent of technologies such as genome-wide chromosome conformation capture (Hi-C), it has become clear that these structures are essential for proper gene regulation, DNA replication, and repair (Hnisz et al., 2016; Dekker andMirny, 2016; Pope et al., 2014; McCord and Balajee, 2018).”
Background3D organization of regulatory elements for transcriptional regulation in Arabidopsis
Deng, L., Zhou, Q., Zhou, J., Zhang, Q., Jia, Z.-B., Zhu, G., Cheng, S., Cheng, L., Yin, C., Yang, C., et al. (2023) · Genome Biology · doi:10.1186/s13059-023-03018-4 · Cited by 27
Li, R., Liu, Y., Li, T., & Li, C. (2016) · Scientific Reports · doi:10.1038/srep34651 · Cited by 39
“In the future, we will expand our method to predict chromatin loops that are disrupted by disease-associated CRs or SNPs such as those in cancer 30 .”
MethodSelf-citationWegner, M., Diehl, V., Bittl, V., de Bruyn, R., Wiechmann, S., Matthess, Y., Hebel, M., Hayes, M. G. B., Schaubeck, S., Benner, C. W., et al. (2019) · eLife · doi:10.7554/elife.42549 · Cited by 38
An oncogenic enhancer encodes selective selenium dependency in AML
Eagle, K., Jiang, Y., Shi, X. E., Li, M., Obholzer, N. D., Hu, T., Perez, M. W., Koren, J. V., Kitano, A., Yi, J. S., et al. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.01.003 · Cited by 40
Salzberg, A. C., Harris‐Becker, A., Popova, E. Y., Keasey, N., Loughran, T. P., Claxton, D. F., & Grigoryev, S. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173723 · Cited by 37
“Recently, it had been shown that many proto-oncogenes reside in insulated chromosomal neighborhoods and often become activated by chromosomal translocation or boundary site mutations [78].”
Willi, M., Yoo, K. H., Reinisch, F., Kuhns, T. M., Lee, H., Wang, C., & Hennighausen, L. G. (2017) · Nature Communications · doi:10.1038/ncomms16069 · Cited by 36
“Current knowledge about biological functions of CTCF sites has been obtained mainly from studies on cell lines and embryonic stem cells (ESCs) 7,10,15,16,18,23–26 .”
Biomolecular condensates in cancer biology
Suzuki, H. I., & Onimaru, K. (2021) · Cancer Science · doi:10.1111/cas.15232 · Cited by 37
Kwon, D. Y., Xu, B., Zhao, Y.-T., Beagan, J. A., Beagan, J. A., Cui, Y., Xu, B., Zaitseva, D., Phillips‐Cremins, J. E., Blendy, J. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27571-3 · Cited by 39
Manipulating the 3D organization of the largest synthetic yeast chromosome
Zhang, W., Lazar‐Stefanita, L., Yamashita, H., Shen, M. J., MITCHELL, L. A., Kurasawa, H., Lobzaev, E., Fanfani, V., Haase, M. A. B., Sun, X., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.10.015 · Cited by 37
Super-enhancers: A new frontier for glioma treatment
Cheng, M., Zhang, Z. W., Ji, X., Xu, Y., Bian, E., & Zhao, B. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188353 · Cited by 35
Xie, T., Danieli‐Mackay, A., Buccarelli, M., Barbieri, M., Papadionysiou, I., D’Alessandris, Q. G., Robens, C., Übelmesser, N., Vinchure, O. S., Lauretti, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48053-2 · Cited by 36
“1g), suggesting that boundary disruption can favor oncogene dysregulation and malignant transformation 17,22,49 .”
BackgroundTAD fusion score: discovery and ranking the contribution of deletions to genome structure
Huynh, L. N., & Hormozdiari, F. (2019) · Genome biology · doi:10.1186/s13059-019-1666-7 · Cited by 35
Effective normalization for copy number variation in Hi-C data
Servant, N., Varoquaux, N., Heard, E., Barillot, E., & Vert, J.-P. (2017) · BMC Bioinformatics · doi:10.1186/s12859-018-2256-5 · Cited by 34
“Lastly, Hnisz et al. [19], Weischenfeldt et al. [20], and Beroukhim et al. [21] show how disruptions in long range DNA looping and genome rearrangements lead to enhancer hijacking and Flavahan et al. [22] link insulator dysfunctions to oncogene activation in cancer.”
BackgroundRevisiting 3D chromatin architecture in cancer development and progression
Feng, Y., & Pauklin, S. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa747 · Cited by 36
“For example, microdeletion eliminates the boundary of Insulated neighbourhoods in T-cell acute lymphoblastic leukemia (T-ALL), which is linked to the proto-oncogene TAL1 activation (83).”
BackgroundHiGlass: Web-based Visual Exploration and Analysis of Genome Interaction MapsPreprint
Kerpedjiev, P., Abdennur, N. A., Lekschas, F., McCallum, C., Dinkla, K., Strobelt, H., Luber, J. M., Ouellette, S., Azhir, A., Kumar, N., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/121889 · Cited by 43
Structure meets function: How chromatin organisation conveys functionality
Ruiz-Velasco, M., & Zaugg, J. B. (2017) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2017.01.003 · Cited by 40
Terranova, C. J., Tang, M., Orouji, E., Maitituoheti, M., Raman, A. T., Amin, S. B., Liu, Z., & Rai, K. (2018) · Journal of Visualized Experiments · doi:10.3791/56972 · Cited by 38
Enhancer reprogramming in tumor progression: a new route towards cancer cell plasticity
Fagnocchi, L., Poli, V., & Zippo, A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2820-1 · Cited by 38
Quantifying the similarity of topological domains across normal and cancer human cell types
Sauerwald, N., & Kingsford, C. (2018) · Bioinform. · doi:10.1093/bioinformatics/bty265 · Cited by 32
Exploration of Coding and Non-coding Variants in Cancer Using GenomePaint
Zhou, X., Wang, J., Patel, J. N., Valentine, M. B., Shao, Y., Newman, S., Sioson, E., Tian, L., Liu, Y., Brady, S. W., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.011 · Cited by 34
“a regulatory CNV causing aberrant cis-activation of its target gene located outside the CNV boundary (Liu et al. 2020; Hnisz et al. 2016; Northcott et al. 2017; Yang et al. 2020).”
BackgroundInfluentialSelf-citationSnetkova, V., & Skok, J. A. (2018) · Epigenomics · doi:10.2217/epi-2017-0157 · Cited by 34
A comparison of topologically associating domain callers over mammals at high resolution
Sefer, E. (2022) · BMC Bioinformatics · doi:10.1186/s12859-022-04674-2 · Cited by 37
Wang, M., Sunkel, B. D., Ray, W. C., & Stanton, B. Z. (2022) · BMC Molecular and Cell Biology · doi:10.1186/s12860-022-00433-6 · Cited by 37
“Observations of noncoding variants in human cancers motivated systematic analyses of altered chromatin loops in cancer cell lines, using Hi-C and ChIA-PET [26].”
BackgroundMethodInfluentialDevelopmental origins shape the paediatric cancer genome
Chen, X., Yang, W., Roberts, C. W. M., & Zhang, J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00684-9 · Cited by 49
“Disruption of boundary sites, mostly by microdeletions, can lead to aberrant oncogene activation such as TAL1 and LMO2 in T-ALL 93 , FLT3 in B-ALL 94 and prolactin receptor ( PRLR ) in T-ALL 95 .”
Probabilistic inference of epigenetic age acceleration from cellular dynamics
Dabrowski, J., Yang, E. J., Crofts, S., Hillary, R. F., Simpson, D. J., McCartney, D. L., Marioni, R. E., Kirschner, K., Crespo, E. L., & Chandra, T. (2024) · Nature Aging · doi:10.1038/s43587-024-00700-5 · Cited by 35
“3e), for which MYCN deficiency is a known risk factor 31,32 .”
BackgroundHigh-resolution dynamic imaging of chromatin DNA communication using Oligo-LiveFISH
Zhu, Y., Balaji, A., Han, M., Andronov, L. P., Roy, A. R., Wei, Z., Chen, C., Miles, L., Cai, S., Gu, Z., et al. (2025) · Cell · doi:10.1016/j.cell.2025.03.032 · Cited by 38
The Many Faces of Gene Regulation in Cancer: A Computational Oncogenomics Outlook
Lemus, E. H., Reyes-Gopar, H., Enríquez, J. E., & Ochoa, S. (2019) · Genes · doi:10.3390/genes10110865 · Cited by 33
Genome-guided discovery of cancer therapeutic targets
Konda, P., Garinet, S., Allen, E. M. V., & Viswanathan, S. R. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112978 · Cited by 36
Structural variants in the 3D genome as drivers of disease
Sreenivasan, V. K. A., Yumiceba, V., & Spielmann, M. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00862-x · Cited by 45
Insights about genome function from spatial organization of the genome
Roy, S. S., Mukherjee, A. K., & Chowdhury, S. (2018) · Human Genomics · doi:10.1186/s40246-018-0140-z · Cited by 32
“Structural variants disrupting CTCF-associated TAD boundaries were noted to allow de novo promoter-enhancer interactions and ectopic gene expression causing limb malformation [71] and oncogenic transformation [72].”
BackgroundTranscriptional networks in acute myeloid leukemia
Thoms, J. A. I., Beck, D., & Pimanda, J. E. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22794 · Cited by 33
The 3D Genome as a Target for Anticancer Therapy
Kantidze, O. L., Gurova, K. V., Studitsky, V. M., & Razin, S. V. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.09.011 · Cited by 36
“At the 3D genome organization level, it is also possible to unite several individual enhancers in a common activating complex, as in the case of super-enhancers (SEs), composed of several functional enhancers [15].”
BackgroundMethodInfluentialThe Number of Transcription Factors at an Enhancer Determines Switch-like Gene Expression
Michida, H., Imoto, H., Shinohara, H., Yumoto, N., Seki, M., Umeda, M., Hayashi, T., Nikaido, I., Kasukawa, T., Suzuki, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107724 · Cited by 35
Galupa, R., & Heard, É. (2017) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2017.82.035030 · Cited by 30
“An excess of somatic mutations at CTCF sites is found in essentially all types of cancers, especially at sites involved in higher- order chromatin structures, such as TAD boundaries (Katainen et al. 2015; Hnisz et al. 2016; Kaiser et al. 2016).”
BackgroundInfluentialMapping oncogenic protein interactions for precision medicine
Tabar, M. S., Francis, H., Yeo, D., Bailey, C. G., & Rasko, J. E. J. (2022) · International Journal of Cancer · doi:10.1002/ijc.33954 · Cited by 30
Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex
Kaye, E. G., Kurbidaeva, A., Wolle, D. G., Aoki, T., Schedl, P. D., & Larschan, E. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00253-17 · Cited by 32
Genome organization at different scales: nature, formation and function
Serizay, J., & Ahringer, J. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2018.03.009 · Cited by 35
“In human and mouse, the inversion, deletion or duplication of TADs or TAD boundaries was shown to alter expression of genes located in the affected TADs, resulting in heart or limb pathologies [39,40], Cook syndrome [41] or cancer susceptibility [42].”
BackgroundBarešić, A., Nash, A. J., Dahoun, T., Howes, O. D., & Lenhard, B. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0518-x · Cited by 33
Bottom-Up Meets Top-Down: The Crossroads of Multiscale Chromatin Modeling
Moller, J., & Pablo, J. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2020.03.014 · Cited by 32
Yuan, C., Chen, H., Tu, S., Huang, H.-Y., Pan, Y., Gui, X., Kuang, M., Shen, X., Zheng, Q., Zhang, Y., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02376-1 · Cited by 31
Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis
Cui, K.-R., Chen, Z.-J., Cao, Y.-Q., Liu, S., Ren, G., Hu, G.-Q., Fang, D.-F., Wei, D., Liu, C.-Y., Zhu, J., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.03.006 · Cited by 30
JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia
Mansour, M. R., He, S., Li, Z., Lobbardi, R., Abraham, B. J., Hug, C. B., Rahman, S., León, T. E., Kuang, Y., Zimmerman, M. W., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20170484 · Cited by 32
“4 C) that resides within the same insulated neighborhood as MCL1 (Hnisz et al., 2016).”
BackgroundSelf-citationCTCF-mediated genome organization and leukemogenesis
Qiu, Y., & Huang, S. (2020) · Leukemia · doi:10.1038/s41375-020-0906-x · Cited by 32
Role of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors
Zhao, Y., Feng, F., Guo, Q., Wang, Y., & Zhao, R. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i34.5074 · Cited by 35
Zhang, Y., Wang, M., & Li, S. C. (2021) · Genome biology · doi:10.1186/s13059-020-02234-6 · Cited by 29
Structure–function relationships explain CTCF zinc finger mutation phenotypes in cancer
Bailey, C. G., Gupta, S. K., Metierre, C., Amarasekera, P. M. S., O’Young, P., Kyaw, W., Laletin, T., Francis, H., Semaan, C., Tabar, M. S., et al. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03946-z · Cited by 31
Shang, X., Shi, Y. Y., He, D., Wang, L., Luo, Q., Deng, C.-H., Qu, Y.-L., Wang, N., & Han, Z. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04291-6 · Cited by 31
CTCF: A misguided jack-of-all-trades in cancer cells
Segueni, J., & Noordermeer, D. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.05.044 · Cited by 31
“A detailed study in T cell acute lymphoblastic leukemia (T-ALL) cells identified micro-deletions near oncogenes that removed CBSs from TAD boundaries [96].”
BackgroundRegulation and Dysregulation of Chromosome Structure in Cancer
Hnisz, D., Schuijers, J., Li, C. H., & Young, R. A. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050134 · Cited by 31
““-” indicates that the strongest motif is oriented from 14 right to left on the bottom (i.e. “-” strand), (data from (Hnisz et al., 2016b)).”
BackgroundInfluentialSelf-citationMolecular Dynamics simulations of the Strings and Binders Switch model of chromatin
Annunziatella, C., Chiariello, A. M., Esposito, A., Bianco, S., Fiorillo, L., & Nicodemi, M. (2018) · Methods · doi:10.1016/j.ymeth.2018.02.024 · Cited by 30
Epigenetic characteristics of the mitotic chromosome in 1D and 3D
Oomen, M. E., & Dekker, J. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1287160 · Cited by 32
“It has been shown for several diseases, like cancer and polydactyly, how alteration in looping interactions is associated with the disease phenotype (Hnisz et al., 2016; Lupianez et al., 2015; Zhao et al., 2009).”
BackgroundSelf-citationHeurteau, A., Perrois, C., Depierre, D., Fosseprez, O., Humbert, J., Schaak, S., & Cuvier, O. (2020) · Genome biology · doi:10.1186/s13059-020-02106-z · Cited by 32
“This may involve long-range contacts between a gene and the regulatory sequences localized in the adjacent TAD [9, 28, 29].”
BackgroundSundararajan, V., Pang, Q. Y., Choolani, M. A., & Huang, R. Y. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00213 · Cited by 29
Malavia, N., Kuche, K., Ghadi, R., & Jain, S. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.12.012 · Cited by 30
Involvement of Thyroid Hormones in Brain Development and Cancer
Schiera, G., Liegro, C. M. D., & Liegro, I. D. (2021) · Cancers · doi:10.3390/cancers13112693 · Cited by 36
“In cancer cells, chromatin organization is indeed altered in many ways [43–46], and these modifications can, for example, allow activation of normally silent proto-oncogenes because of loss of an insulated boundary [47].”
BackgroundChakraborty, C., Nissen, I., Vincent, C. A., Hägglund, A., Hörnblad, A., & Remeseiro, S. (2023) · Nature Communications · doi:10.1038/s41467-023-41919-x · Cited by 30
Hijacked enhancer–promoter and silencer–promoter loops in cancer
Wang, X., & Yue, F. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102199 · Cited by 32
Nucleome Analysis Reveals Structure–Function Relationships for Colon Cancer
Seaman, L., Chen, H., Brown, M. A., Wangsa, D., Patterson, G., Camps, J., Omenn, G. S., Ried, T., & Rajapakse, I. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0374 · Cited by 28
“Previous studies of cancer genomes using Hi-C showed long range interactions between known risk loci for the development of colorectal cancer (CRC) and regulatory regions (8), demonstrated proto-oncogene activation by disruption of chromosome neighborhoods (9), determined changes in inter-chromosomal interaction frequ…”
Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization
McCole, R. B., Erceg, J., Saylor, W., & Wu, C.-T. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.031 · Cited by 30
Determinants and role of chromatin organization in acute leukemia
Fang, C., Rao, S., Crispino, J. D., & Ntziachristos, P. (2020) · Leukemia · doi:10.1038/s41375-020-0981-z · Cited by 30
“Short-DNA loops delineated by CCCTC-binding factor (CTCF) and the cohesin-complex are typically constrained within formations called insulated neighborhoods (IN) [8, 9], which can in turn form clusters, leading to topologically associating domains (TADs).”
BackgroundTopological isolation of developmental regulators in mammalian genomes
Wu, H., Landshammer, A., Stamenova, E. K., Bolondi, A., Kretzmer, H., Meissner, A., & Michor, F. (2021) · Nature Communications · doi:10.1038/s41467-021-24951-7 · Cited by 29
Eid, R. A., Soltan, M. A., Eldeen, M. A., Shati, A. A., Dawood, S. A., Eissa, M., Zaki, M. S. A., Algahtani, M., Theyab, A., Abdel‐Daim, M. M., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214102 · Cited by 29
“Hence, a deep study of different oncogenes is an essential process to explore the molecular mechanisms of several genes in cancer development [3].”
BackgroundEmerging roles of noncoding RNAs in human cancers
Wu, S., Wu, Y., Deng, S., Lei, X., & Yang, X. (2023) · Discover Oncology · doi:10.1007/s12672-023-00728-w · Cited by 30
Perturb-tracing enables high-content screening of multi-scale 3D genome regulators
Cheng, Y., Hu, M., Yang, B., Jensen, T. B., Zhang, Y., Yang, T., Yu, R., Ma, Z., Radda, J. S. D., Jin, S., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02652-z · Cited by 31
Korkmaz, G., Manber, Z., Lopes, R., Preković, S., Schuurman, K. G., Kim, Y., Teunissen, H., Flach, K. D., de Wit, E., Galli, G. G., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz675 · Cited by 29
“Though applied to specific CTCF loci of interest before (27,34), a genome-wide CRISPR-Cas9 screen systematically targeting CTCF sites was not yet implemented.”
BackgroundEnhancer-gene rewiring in the pathogenesis of Quebec Platelet Disorder
Liang, M., Soomro, A., Tasneem, S., Abatti, L. E., Alizada, A., Yuan, X., Uusküla-Reimand, L., Antounians, L., Alvi, S. A., Paterson, A. D., et al. (2020) · Blood · doi:10.1182/blood.2020005394 · Cited by 30
Transcription organizes euchromatin similar to an active microemulsionPreprint
Hilbert, L., Sato, Y., Kimurâ, H., Jülicher, F., Honigmann, A., Zaburdaev, V., & Vastenhouw, N. L. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/234112 · Cited by 31
CRISPR Tools for Systematic Studies of RNA RegulationPreprint
Engreitz, J., Abudayyeh, O. O., Gootenberg, J. S., & Zhang, F. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035386 · Cited by 31
“…CRISPR-based studies of individual CTCF sites have revealed that these sites do indeed control 3D contacts and gene expression, perhaps by tuning the contacts between genes and their enhancers (de Wit et al. 2015; Guo et al. 2015; Sanborn et al. 2015; Flavahan et al. 2016; Hnisz et al. 2016).”
BackgroundEvolution and function of chromatin domains across the tree of life
Szalay, M.-F., Majchrzycka, B., Jerković, I., Cavalli, G., & Ibrahim, D. M. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01427-y · Cited by 31
Enhancer RNAs: Insights Into Their Biological Role
de Lara, J. C.-F., Arzate‐Mejía, R. G., & Targa, F. R. (2019) · Epigenetics Insights · doi:10.1177/2516865719846093 · Cited by 28
A guide to visualizing the spatial epigenome with super‐resolution microscopy
Xu, J., & Liu, Y. (2019) · FEBS Journal · doi:10.1111/febs.14938 · Cited by 30
Tidying-up the plant nuclear space: domains, functions, and dynamics
Santos, A. P., Gaudin, V., Mozgová, I., Pontvianne, F., Schubert, D. S. P., Tek, A. L., Dvořáčková, M., Liu, C., Fransz, P. F., Rosa, S., et al. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa282 · Cited by 29
The X chromosome in C. elegans sex determination and dosage compensation
Meyer, B. J. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101912 · Cited by 27
Ling, X., Liu, X., Jiang, S., Fan, L., & Ding, J. (2022) · Cell Regeneration · doi:10.1186/s13619-022-00145-4 · Cited by 29
Contessoto, V. G., Dudchenko, O., Aiden, E. L., Wolynes, P. G., Onuchic, J. N., & Pierro, M. D. (2023) · Nature Communications · doi:10.1038/s41467-023-35909-2 · Cited by 27
Spatial promoter–enhancer hubs in cancer: organization, regulation, and function
Zhao, J., & Faryabi, R. B. (2023) · Trends in Cancer · doi:10.1016/j.trecan.2023.07.017 · Cited by 28
Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae
Cheng, L. E., Zhao, S., Li, T., Hou, S., Luo, Z., Xu, J., Yu, W., Jiang, S., Monti, M., Schindler, D., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44511-5 · Cited by 30
Haider, Z., Larsson, P. G., Landfors, M., Köhn, L., Schmiegelow, K., Flægstad, T., Kanerva, J. A., Heyman, M. M., Hultdin, M., & Degerman, S. (2018) · Cancer Medicine · doi:10.1002/cam4.1917 · Cited by 28
The Cancer-Associated Genetic Variant Rs3903072 Modulates Immune Cells in the Tumor Microenvironment
Zhang, Y., Manjunath, M., Yan, J., Baur, B. A., Zhang, S., Roy, S., & Song, J. S. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00754 · Cited by 27
Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription
Shaban, H. A., Barth, R., & Bystricky, K. (2020) · Genome biology · doi:10.1186/s13059-020-02185-y · Cited by 28
Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction
Pennacchio, F. A., Nastały, P., Poli, A., & Maiuri, P. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.596746 · Cited by 26
Spatial Organization of Chromatin: Transcriptional Control of Adaptive Immune Cell Development
Pongubala, J. M. R., & Murre, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633825 · Cited by 29
“Another prominent example Frontiers in Immunology | www.frontiersin.org 6 is where perturbation of CTCF-associated boundary elements results in increased activation of proto-oncogenes that are frequently associated with T-cell acute-lymphoblastic leukemia (T-ALL) (120).”
BackgroundDynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer
Du, Y., Gu, Z., Li, Z., Yuan, Z., Zhao, Y., Zheng, X., Bo, X., Chen, H., & Wang, C. (2022) · Advanced Science · doi:10.1002/advs.202200818 · Cited by 28
Predicting 3D chromatin interactions from DNA sequence using Deep Learning
Piecyk, R. S., Schlegel, L., & Johannes, F. M. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.06.047 · Cited by 27
“Building on the above-describe approach, several studies have tried to test or identify specific loop-disrupting genetic variants and their impact on cancerogenesis [39].”
ResultCTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
Zhou, R., Tian, K., Huang, J. S., Duan, W., Fu, H., Feng, Y., Wang, H., Jiang, Y., Li, Y., Wang, R., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105011 · Cited by 26
Function and Evolution of the Loop Extrusion Machinery in Animals
Kabirova, E., Nurislamov, A. R., Shadskiy, A., Smirnov, A. V., Popov, A., Salnikov, P., Баттулин, Н. Р., & Fishman, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055017 · Cited by 27
Metadata
- Authors
- Hnisz, D., Weintraub, A. S., Day, D. S., Valton, A.-L., Bak, R. O., Li, C. H., Goldmann, J., Lajoie, B. R., Fan, Z. P., Sigova, A. A., Reddy, J., Borges-Rivera, D., Lee, T. I., Jaenisch, R., Porteus, M. H., Dekker, J., & Young, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- University of Massachusetts Chan Medical School (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hnisz, Denes
- Weintraub, Abraham S.
- Young, Richard A.
- ORCID
- Venue
- Science
- Published
- 2016-03-25
- Volume
- 351
- Issue
- 6280
- Pages
- 1454-1458
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4884612
- OpenAlex
- W2303393194
- Cited by
- 1,042
- References
- 73
- Citations by year
- 2026: 48 · 2025: 67 · 2024: 90 · 2023: 106 · 2022: 90 · 2021: 124 · 2020: 129 · 2019: 132 · 2018: 102 · 2017: 104 · 2016: 48
- FWCI
- 66.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- HAL (submittedVersion)
- Funders
- Austrian Science Fund (J3490)
- Ludwig Graduate Fellowship
- Laurie Kraus Lacob Faculty Scholar Award in Pediatric Translational Research
- Hyundai Hope on Wheels
- Danish Council for Independent Research, Medical Sciences
- Sapere Aude Research Talent (DFF-1331-00735B)
- National Human Genome Research Institute (R01 HG003143, U54 HG007010, U01 HG007910)
- National Cancer Institute (U54 CA193419)
- NIH (HG002668, CA109901, NS088538, MH104610, AI120766, U54 DK107980, U01 DA 040588)
- National Institute of General Medical Sciences (R01 GM 112720)
- National Institute of Allergy and Infectious Diseases (U01 R01 AI 117839)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- proto-oncogenes, oncogene activation, T-cell acute lymphoblastic leukemia, microdeletion, chromosome structure, cancer genetics, gene expression regulation
- MeSH terms
- Chromosome Aberrations, Chromosome Mapping, Humans, Mutation, Proto-Oncogenes, Translocation, Genetic, Transcriptional Activation, Gene Expression Regulation, Leukemic, Sequence Deletion, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, HEK293 Cells
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