How subtle changes in 3D structure can create large changes in transcription

Xiao, Jordan Yupeng; Hafner, Antonina; Boettiger, Alistair N

doi:10.7554/elife.64320

Cited by 162Genomics and Chromatin DynamicsGene Regulatory Network AnalysisProtein Structure and Dynamics

How subtle changes in 3D structure can create large changes in transcription

Open access

Xiao, Jordan Yupeng, Hafner, Antonina, Boettiger, Alistair N·2021·eLife

DOI 10.7554/elife.64320PMC PMC8352591

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Animal genomes are organized into topologically associated domains (TADs). TADs are thought to contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and preventing these contacts across TAD borders. However, the absolute difference in contact frequency across TAD boundaries is usually less than 2-fold, even though disruptions of TAD borders can change gene expression by 10-fold. Existing models fail to explain this hypersensitive response. Here, we propose a futile cycle model of enhancer-mediated regulation that can exhibit hypersensitivity through bistability and hysteresis. Consistent with recent experiments, this regulation does not exhibit strong correlation between E-P contact and promoter activity, even though regulation occurs through contact. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of E-P biochemical specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile apparently contradictory results from recent global TAD disruption with local TAD boundary deletion experiments. Together, these analyses advance our understanding of cis-regulatory contacts in controlling gene expression and suggest new experimental directions.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.7554/elife.64320

Cites

107 of 107 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Reducing the dose of dox tunes the effective rTetR-VP48 concentration as measured in vitro by an Electrophoretic Mobility Shift Assay.
“By reducing the dose of dox, we tuned the effective rTetR-VP48 concentration36 as measured in vitro by an Electrophoretic Mobility Shift Assay (Fig. S4L–O)”
From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [36]
The Materials and methods section discusses transcription-factor concentration and enhancer occupancy only in general terms. Searches for rTetR-VP48, doxycycline or dox, and electrophoretic mobility shift assays found no passage in our copy addressing whether reducing dox tunes effective rTetR-VP48 concentration or how that was measured. The copy provides no page numbers for these passages. (LLM, conf=0.75)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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 · see citing works
Molecular Biology of the Cell
Alberts, B., Johnson, A., Lewis, J. H., Morgan, D. O., RAFF, M. C., Roberts, K. J., & Walter, P. (2017) · W.W. Norton eBooks · doi:10.1201/9781315735368 · Cited by 7,937 · see citing works
Topological 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 · see citing works
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895 · see citing works
Coactivator condensation at super-enhancers links phase separation and gene control
Sabari, B. R., Dall’Agnese, A., Boija, A., Klein, I. A., Coffey, E. L., Shrinivas, K., Abraham, B. J., Hannett, N. M., Zamudio, A. V., Manteiga, J. C., et al. (2018) · Science · doi:10.1126/science.aar3958 · Cited by 2,595 · see citing works
Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom
Durand, N. C., Robinson, J., Shamim, M. S., Machol, I., Mesirov, J. P., Lander, E. S., & Aiden, E. L. (2016) · Cell Systems · doi:10.1016/j.cels.2015.07.012 · Cited by 2,335 · see citing works
Nonlinear Dynamics and Chaos
Strogatz, S. H. (2018) · CRC Press eBooks · doi:10.1201/9780429492563 · Cited by 2,247 · see citing works
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Lupiáñez, D. G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J. M., Laxova, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.004 · Cited by 2,132 · see citing works
Mediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939 · see citing works
Cohesin Loss Eliminates All Loop Domains
Rao, S. S. P., Huang, S.-C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K.-R., Sanborn, A. L., Johnstone, S. E., Bascom, G. D., Bochkov, I. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.026 · Cited by 1,883 · see citing works
Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization
Nora, E. P., Goloborodko, A., Valton, A.-L., Gibcus, J. H., Uebersohn, A., Abdennur, N., Dekker, J., Mirny, L. A., & Bruneau, B. G. (2017) · Cell · doi:10.1016/j.cell.2017.05.004 · Cited by 1,709 · cited 2× · see citing works
“However, global disruption of TAD boundaries by depletion of boundary associated factors led to few substantial changes in gene expression in cell culture models (Nora et al., 2017; Rao et al., 2017; Schwarzer et al., 2017), contradicting the earlier studies.”
BackgroundResult
Mediator and RNA polymerase II clusters associate in transcription-dependent condensates
Cho, W.-K., Spille, J.-H., Hecht, M., Lee, C., Li, C., Grube, V., & Cisse, I. I. (2018) · Science · doi:10.1126/science.aar4199 · Cited by 1,403 · see citing works
Two independent modes of chromatin organization revealed by cohesin removal
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., et al. (2017) · Nature · doi:10.1038/nature24281 · Cited by 1,196 · see citing works
Ultrasensitivity in the mitogen-activated protein kinase cascade.
Huang, C. Y., & Ferrell, J. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10078 · Cited by 1,186 · see citing works
Organizational principles of 3D genome architecture
Rowley, M. J., & Corces, V. G. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0060-8 · Cited by 1,171 · see citing works
A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly
Lettice, L. A. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg180 · Cited by 1,164 · see citing works
HiChIP: efficient and sensitive analysis of protein-directed genome architecture
Mumbach, M. R., Rubin, A. J., Flynn, R. A., Dai, C., Khavari, P. A., Greenleaf, W. J., & Chang, H. Y. (2016) · Nature Methods · doi:10.1038/nmeth.3999 · Cited by 1,139 · see citing works
Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq
Arnold, C. D., Gerlach, D., Stelzer, C., Boryń, Ł. M., Rath, M., & Stark, A. (2013) · Science · doi:10.1126/science.1232542 · Cited by 1,125 · see citing works
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting
Schuettengruber, B., Bourbon, H.-M., Di Croce, L., & Cavalli, G. (2017) · Cell · doi:10.1016/j.cell.2017.08.002 · Cited by 1,094 · see citing works
Multistability in the lactose utilization network of Escherichia coli
Ozbudak, E. M., Thattai, M., Lim, H. N., Shraiman, B. I., & van Oudenaarden, A. (2004) · Nature · doi:10.1038/nature02298 · Cited by 1,030 · see citing works
Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells
Bintu, B., Mateo, L. J., Su, J.-H., Sinnott-Armstrong, N. A., Parker, M., Kinrot, S., Yamaya, K., Boettiger, A. N., & Zhuang, X. (2018) · Science · doi:10.1126/science.aau1783 · Cited by 976 · see citing works
Self-citation
Imaging dynamic and selective low-complexity domain interactions that control gene transcription
Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., et al. (2018) · Science · doi:10.1126/science.aar2555 · Cited by 966 · see citing works
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function
Guo, Y., Xu, Q., Canzio, D., Shou, J., Li, J., Gorkin, D. U., Jung, I., Wu, H., Zhai, Y., Tang, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.038 · Cited by 958 · see citing works
Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution
Long, H. K., Prescott, S. L., & Wysocka, J. (2016) · Cell · doi:10.1016/j.cell.2016.09.018 · Cited by 945 · see citing works
Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus
Quinodoz, S. A., Ollikainen, N., Tabak, B., Palla, A., Schmidt, J. M., Detmar, E., Lai, M. M., Shishkin, A. A., Bhat, P., Takei, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.024 · Cited by 892 · see citing works
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes
Dowen, J. M., Fan, Z. P., Hnisz, D., Ren, G., Abraham, B. J., Zhang, L. N., Weintraub, A. S., Schuijers, J., Lee, T. I., Zhao, K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.030 · Cited by 884 · see citing works
Transcriptional regulation by the numbers: models
Bintu, L., Buchler, N. E. G., García, H. G., Gerland, U., Terence Hwa, B., Kondev, J., & Phillips, R. (2005) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2005.02.007 · Cited by 784 · see citing works
Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells
Zuin, J., Dixon, J. R., van der Reijden, M. I. J. A., Ye, Z., Kolovos, P., Brouwer, R. W. W., van de Corput, M. P. C., van de Werken, H. J. G., Knoch, T. A., van IJcken, W. F. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317788111 · Cited by 779 · see citing works
Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor
Deng, W., Lee, J., Wang, H., Miller, J., Reik, A., Gregory, P. D., Dean, A., & Blobel, G. A. (2012) · Cell · doi:10.1016/j.cell.2012.03.051 · Cited by 734 · see citing works
Structural variation in the 3D genome
Spielmann, M., Lupiáñez, D. G., & Mundlos, S. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0007-0 · Cited by 719 · see citing works
Complex multi-enhancer contacts captured by genome architecture mapping
Beagrie, R. A., Scialdone, A., Schueler, M., Kraemer, D. C. A., Chotalia, M., Xie, S. Q., Barbieri, M., de Santiago, I., Lavitas, L.-M., Branco, M. R., et al. (2017) · Nature · doi:10.1038/nature21411 · Cited by 715 · see citing works
Probing the Limits to Positional Information
Gregor, T., Tank, D. W., Wieschaus, E. F., & Bialek, W. (2007) · Cell · doi:10.1016/j.cell.2007.05.025 · Cited by 681 · see citing works
Pol II phosphorylation regulates a switch between transcriptional and splicing condensates
Guo, Y. E., Manteiga, J. C., Henninger, J. E., Sabari, B. R., Dall’Agnese, A., Hannett, N. M., Spille, J.-H., Afeyan, L. K., Zamudio, A. V., Shrinivas, K., et al. (2019) · Nature · doi:10.1038/s41586-019-1464-0 · Cited by 676 · see citing works
Formation of new chromatin domains determines pathogenicity of genomic duplications
Franke, M., Ibrahim, D. M., Andrey, G., Schwarzer, W., Heinrich, V., Schöpflin, R., Kraft, K., Kempfer, R., Jerković, I., Chan, W.-L., et al. (2016) · Nature · doi:10.1038/nature19800 · Cited by 673 · see citing works
Nonlinear Dynamics and Chaos with Student Solutions Manual: With Applications to Physics, Biology, Chemistry, and Engineering, Second Edition
Strogatz, S. H. (2018) · doi:10.1201/9780429399640 · Cited by 654 · see citing works
Developmental enhancers and chromosome topology
Furlong, E. E. M., & Levine, M. (2018) · Science · doi:10.1126/science.aau0320 · Cited by 641 · see citing works
Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II
Lu, H., Yu, D., Hansen, A. S., Ganguly, S., Liu, R., Heckert, A. B., Darzacq, X., & Zhou, Q. (2018) · Nature · doi:10.1038/s41586-018-0174-3 · Cited by 576 · see citing works
Epigenetic balance of gene expression by Polycomb and COMPASS families
Piunti, A., & Shilatifard, A. (2016) · Science · doi:10.1126/science.aad9780 · Cited by 524 · see citing works
Methods for mapping 3D chromosome architecture
Kempfer, R., & Pombo, A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0195-2 · Cited by 502 · see citing works
Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements
Mumbach, M. R., Satpathy, A. T., Boyle, E. A., Dai, C., Gowen, B. G., Cho, S. W., Nguyen, M. L., Rubin, A. J., Granja, J. M., Kazane, K. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3963 · Cited by 490 · cited 1× · see citing works
“…should colocalize with their active enhancers, based largely on bulk population assays such 3C and H3K27ac Hi-Chip (Bartman et al., 2016; Deng et al., 2012; Kagey et al., 2010; Mumbach et al., 2017, 2016; Rao et al., 2014; Williamson et al., 2016), for review see (Furlong and Levine, 2018).”
Background
Real-Time Dynamics of RNA Polymerase II Clustering in Live Human Cells
Cissé, I. I., Izeddin, I., Causse, S., Boudarène, L., Senecal, A., Mureşan, L., Dugast‐Darzacq, C., Hajj, B., Dahan, M., & Darzacq, X. (2013) · Science · doi:10.1126/science.1239053 · Cited by 489 · see citing works
Robustness of the BMP morphogen gradient in Drosophila embryonic patterning
Eldar, A., Dorfman, R., Weiss, D., Ashe, H. L., Shilo, B., & Barkai, N. (2002) · Nature · doi:10.1038/nature01061 · Cited by 465 · see citing works
Functional and topological characteristics of mammalian regulatory domains
Symmons, O., Uslu, V. V., Tsujimura, T., Ruf, S., Nassari, S., Schwarzer, W., Ettwiller, L., & Spitz, F. (2014) · Genome Research · doi:10.1101/gr.163519.113 · Cited by 455 · see citing works
Visualizing DNA folding and RNA in embryos at single-cell resolution
Mateo, L. J., Murphy, S. E., Hafner, A., Cinquini, I. S., Walker, C. A., & Boettiger, A. N. (2019) · Nature · doi:10.1038/s41586-019-1035-4 · Cited by 446 · see citing works
Self-citation
Dynamics and Memory of Heterochromatin in Living Cells
Hathaway, N. A., Bell, O., Hodges, C., Miller, E. L., Neel, D. S., & Crabtree, G. R. (2012) · Cell · doi:10.1016/j.cell.2012.03.052 · Cited by 446 · see citing works
Genome-scale functional characterization of Drosophila developmental enhancers in vivo
Kvon, E. Z., Kazmar, T., Stampfel, G., Yáñez-Cuna, J. O., Pagani, M., Schernhuber, K., Dickson, B. J., & Stark, A. (2014) · Nature · doi:10.1038/nature13395 · Cited by 436 · see citing works
Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control
Hnisz, D., Day, D. S., & Young, R. A. (2016) · Cell · doi:10.1016/j.cell.2016.10.024 · Cited by 420 · see citing works
Nonlinear control of transcription through enhancer–promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2022) · Nature · doi:10.1038/s41586-022-04570-y · Cited by 415 · see citing works
Transcriptional regulation by the numbers: applications
Bintu, L., Buchler, N. E. G., García, H. G., Gerland, U., Terence Hwa, B., Kondev, J., Kuhlman, T. E., & Phillips, R. (2005) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2005.02.006 · Cited by 403 · see citing works
Shadow Enhancers Foster Robustness of Drosophila Gastrulation
Perry, M. W., Boettiger, A. N., Bothma, J. P., & Levine, M. (2010) · Current Biology · doi:10.1016/j.cub.2010.07.043 · Cited by 396 · see citing works
Self-citation
Bistability, Bifurcations, and Waddington's Epigenetic Landscape
Ferrell, J. E. (2012) · Current Biology · doi:10.1016/j.cub.2012.03.045 · Cited by 380 · see citing works
Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019) · Nature Genetics · doi:10.1038/s41588-019-0462-3 · Cited by 354 · see citing works
Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
Alexander, J. M., Guan, J., Li, B., Maliskova, L., Song, M., Shen, Y., Huang, B., Lomvardas, S., & Weiner, O. D. (2019) · eLife · doi:10.7554/elife.41769 · Cited by 346 · see citing works
Enhancer Regulation of Transcriptional Bursting Parameters Revealed by Forced Chromatin Looping
Bartman, C. R., Hsu, S. C., Hsiung, C. C.-S., Raj, A., & Blobel, G. A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.007 · Cited by 345 · see citing works
Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation
Benabdallah, N. S., Williamson, I., Illingworth, R. S., Kane, L., Boyle, S., Sengupta, D., Grimes, G. R., Therizols, P., & Bickmore, W. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.038 · Cited by 335 · see citing works
Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture
Despang, A., Schöpflin, R., Franke, M., Ali, S., Jerković, I., Paliou, C., Chan, W.-L., Timmermann, B., Wittler, L., Vingron, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0466-z · Cited by 306 · see citing works
Kinetics of phase transitions: Theory of Ostwald ripening
Marqusee, J. A., & Ross, J. R. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445532 · Cited by 284 · see citing works
Molecular basis and biological function of variability in spatial genome organization
Finn, E. H., & Misteli, T. (2019) · Science · doi:10.1126/science.aaw9498 · Cited by 270 · see citing works
Dimeric ligands define a role for transcriptional activation domains in reinitiation
Ho, S. N., Biggar, S. R., Spencer, D. M., Schreiber, S. L., & Crabtree, G. R. (1996) · Nature · doi:10.1038/382822a0 · Cited by 261 · see citing works
Essentials of Stochastic Processes
Durrett, R. T. (2012) · Springer texts in statistics · doi:10.1007/978-1-4614-3615-7 · Cited by 257 · see citing works
Enhancer hubs and loop collisions identified from single-allele topologies
Allahyar, A., Vermeulen, C., Bouwman, B. A. M., Krijger, P. H. L., Verstegen, M. J. A. M., Geeven, G., van Kranenburg, M., Pieterse, M., Straver, R., Haarhuis, J. H. I., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0161-5 · Cited by 227 · see citing works
The liquid nucleome – phase transitions in the nucleus at a glance
Strom, A. R., & Brangwynne, C. P. (2019) · Journal of Cell Science · doi:10.1242/jcs.235093 · Cited by 223 · see citing works
Canalization of Gene Expression and Domain Shifts in the Drosophila Blastoderm by Dynamical Attractors
Manu, Surkova, S. Y., Spirov, A. V., Gursky, V. V., Janssens, H., Kim, A.-R., Radulescu, O., Vanario‐Alonso, C. E., Sharp, D. H., Samsonova, M. G., et al. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000303 · Cited by 211 · see citing works
Bistability and Oscillations in the Huang-Ferrell Model of MAPK Signaling
Qiao, L., Nachbar, R. B., Kevrekidis, I. G., & Shvartsman, S. Y. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030184 · Cited by 210 · see citing works
Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation
Cuartero, S., Weiss, F. D., Dharmalingam, G., Guo, Y., Ing-Simmons, E., Masella, S., Robles-Rebollo, I., Xiao, X., Wang, Y.-F., Barozzi, I., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0184-1 · Cited by 210 · see citing works
Chromosome Conformation Capture and Beyond: Toward an Integrative View of Chromosome Structure and Function
McCord, R. P., Kaplan, N., & Giorgetti, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.021 · Cited by 204 · see citing works
Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
Oudelaar, A. M., Davies, J. O. J., Hanssen, L. L. P., Telenius, J. M., Schwessinger, R., Liu, Y., Brown, J. M., Downes, D. J., Chiariello, A. M., Bianco, S., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0253-2 · Cited by 196 · see citing works
Pre-Steady-State Decoding of the Bicoid Morphogen Gradient
Bergmann, S., Sandler, O., Sberro, H., Shnider, S. J., Schejter, E. D., Shilo, B., & Barkai, N. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050046 · Cited by 195 · see citing works
In search of the determinants of enhancer–promoter interaction specificity
van Arensbergen, J., van Steensel, B., & Bussemaker, H. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.004 · Cited by 172 · see citing works
Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression
He, X., Samee, M. A. H., Blatti, C. A., & Sinha, S. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000935 · Cited by 171 · see citing works
A Mechanism for Coordinating Chromatin Modification and Preinitiation Complex Assembly
Black, J. C., Choi, J. E., Lombardo, S. R., & Carey, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.018 · Cited by 168 · see citing works
The bx region enhancer, a distant cis‐control element of the Drosophila Ubx gene and its regulation by hunchback and other segmentation genes.
Qian, S., Capovilla, M., & Pirrotta, V. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07662.x · Cited by 166 · see citing works
Computational Models for Neurogenic Gene Expression in the Drosophila Embryo
Zinzen, R. P., Senger, K., Levine, M., & Papatsenko, D. (2006) · Current Biology · doi:10.1016/j.cub.2006.05.044 · Cited by 165 · see citing works
Long range repression conferring boundaries of Ultrabithorax expression in the Drosophila embryo.
Müller, J., & Bienz, M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04876.x · Cited by 165 · see citing works
Preformed chromatin topology assists transcriptional robustness of Shh during limb development
Paliou, C., Guckelberger, P., Schöpflin, R., Heinrich, V., Esposito, A., Chiariello, A. M., Bianco, S., Annunziatella, C., Helmuth, J., Haas, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900672116 · Cited by 163 · see citing works
Rapid and reversible epigenome editing by endogenous chromatin regulators
Braun, S. M. G., Kirkland, J. G., Chory, E. J., Husmann, D., Calarco, J. P., & Crabtree, G. R. (2017) · Nature Communications · doi:10.1038/s41467-017-00644-y · Cited by 158 · see citing works
Enhancer-promoter communication: hubs or loops?
Lim, B., & Levine, M. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.10.001 · Cited by 149 · see citing works
Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression
Sánchez, Á., García, H. G., Jones, D., Phillips, R., & Kondev, J. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1001100 · Cited by 144 · see citing works
An Integrated Holo-Enhancer Unit Defines Tissue and Gene Specificity of the Fgf8 Regulatory Landscape
Marinić, M., Aktaş, T., Ruf, S., & Spitz, F. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.01.025 · Cited by 142 · see citing works
Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries
Gong, Y., Lazaris, C., Sakellaropoulos, T., Lozano, A. C., Kambadur, P., Ntziachristos, P., Aifantis, I., & Tsirigos, A. (2018) · Nature Communications · doi:10.1038/s41467-018-03017-1 · Cited by 140 · see citing works
CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response
Stik, G., Vidal, E., Barrero, M., Cuartero, S., Vila-Casadesús, M., Mendieta-Esteban, J., Tian, T. V., Choi, J., Berenguer, C., Abad, A., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0643-0 · Cited by 139 · see citing works
Developmentally regulated Shh expression is robust to TAD perturbations
Williamson, I., Kane, L., Devenney, P. S., Flyamer, I. M., Anderson, E., Kilanowski, F. M., Hill, R. E., Bickmore, W. A., & Lettice, L. A. (2019) · Development · doi:10.1242/dev.179523 · Cited by 132 · see citing works
Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity
Williamson, I., Lettice, L. A., Hill, R. E., & Bickmore, W. A. (2016) · Development · doi:10.1242/dev.139188 · Cited by 124 · see citing works
Transcriptional cofactors display specificity for distinct types of core promoters
Haberle, V., Arnold, C. D., Pagani, M., Rath, M., Schernhuber, K., & Stark, A. (2019) · Nature · doi:10.1038/s41586-019-1210-7 · Cited by 123 · see citing works
Chromatin topology, condensates and gene regulation: shifting paradigms or just a phase?
Mir, M., Bickmore, W. A., Furlong, E. E. M., & Narlikar, G. J. (2019) · Development · doi:10.1242/dev.182766 · Cited by 109 · see citing works
To loop or not to loop: what is the role of TADs in enhancer function and gene regulation?
Cavalheiro, G. R., Pollex, T., & Furlong, E. E. M. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.015 · Cited by 101 · see citing works
Modeling the dynamics of transcriptional gene regulatory networks for animal development
Ben-Tabou de-Leon, S., & Davidson, E. H. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2008.10.043 · Cited by 99 · see citing works
Visualizing the Role of Boundary Elements in Enhancer-Promoter Communication
Yokoshi, M., Kazuma, S., & Fukaya, T. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.02.007 · Cited by 89 · see citing works
Large distances separate coregulated genes in living Drosophila embryos
Heist, T., Fukaya, T., & Levine, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908962116 · Cited by 89 · see citing works
The large upstream control region of the Drosophila homeotic gene Ultrabithorax
Irvine, K. D., Helfand, S. L., & Hogness, D. S. (1991) · Development · doi:10.1242/dev.111.2.407 · Cited by 88 · see citing works
DamC reveals principles of chromatin folding in vivo without crosslinking and ligation
Redolfi, J., Zhan, Y., Valdes-Quezada, C., Kryzhanovska, M., Guerreiro, I., Iesmantavicius, V., Pollex, T., Grand, R. S., Mulugeta, E., Kind, J., et al. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0231-0 · Cited by 86 · see citing works
HiC-bench: comprehensive and reproducible Hi-C data analysis designed for parameter exploration and benchmarking
Lazaris, C., Kelly, S. M., Ntziachristos, P., Aifantis, I., & Tsirigos, A. (2016) · BMC Genomics · doi:10.1186/s12864-016-3387-6 · Cited by 83 · see citing works
A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus
Oudelaar, A. M., Harrold, C. L., Hanssen, L. L. P., Telenius, J. M., Higgs, D. R., & Hughes, J. R. (2019) · Nature Communications · doi:10.1038/s41467-019-13404-x · Cited by 80 · see citing works
The role of 3D chromatin domains in gene regulation: a multi-facetted view on genome organization
Ibrahim, D. M., & Mundlos, S. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.02.015 · Cited by 79 · see citing works
Using transgenic reporter assays to functionally characterize enhancers in animals
Kvon, E. Z. (2015) · Genomics · doi:10.1016/j.ygeno.2015.06.007 · Cited by 73 · see citing works
Nonlinear control of transcription through enhancer-promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2021) · doi:10.1101/2021.04.22.440891 · Cited by 67 · see citing works
Higher-Order Chromosomal Structures Mediate Genome Function
Jerković, I., Szabo, Q., Bantignies, F., & Cavalli, G. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.014 · Cited by 55 · see citing works
Genomic environments scale the activities of diverse core promotersPreprint
Hong, C. K., & Cohen, B. A. (2021) · Genome Research · doi:10.1101/gr.276025.121 · Cited by 51 · see citing works
Self-Organized Shuttling: Generating Sharp Dorsoventral Polarity in the Early Drosophila Embryo
Haskel‐Ittah, M., Ben‐Zvi, D., Branski-Arieli, M., Schejter, E. D., Shilo, B., & Barkai, N. (2012) · Cell · doi:10.1016/j.cell.2012.06.044 · Cited by 50 · see citing works
The architecture of gene expression: integrating dispersed cis-regulatory modules into coherent regulatory domains
Schwarzer, W., & Spitz, F. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.03.014 · Cited by 49 · see citing works
The CBX family of proteins in transcriptional repression and memory
Kim, J. J., & Kingston, R. E. (2020) · Journal of Biosciences · doi:10.1007/s12038-019-9972-5 · Cited by 43 · see citing works
Enhancer Responses to Similarly Distributed Antagonistic Gradients in Development
Zinzen, R. P., & Papatsenko, D. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030084 · Cited by 40 · see citing works
Transcriptional precision and accuracy in development: from measurements to models and mechanisms
Bentovim, L., Harden, T. T., & DePace, A. H. (2017) · Development · doi:10.1242/dev.146563 · Cited by 39 · see citing works
Liquid-like interactions in heterochromatin: Implications for mechanism and regulation
Sanulli, S., & Narlikar, G. J. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.03.004 · Cited by 35 · see citing works
Recent advances in the spatial organization of the mammalian genome
Kumar, Y., Sengupta, D., & Bickmore, W. A. (2020) · Journal of Biosciences · doi:10.1007/s12038-019-9968-1 · Cited by 15 · see citing works
A genome disconnect
Finn, E. H., & Misteli, T. (2019) · Nature Genetics · doi:10.1038/s41588-019-0476-x · Cited by 14 · see citing works
エンハンサー-プロモーターコミュニケーションにおける境界要素の役割の可視化【JST・京大機械翻訳】
Yokoshi, M., Kazuma, S., & Takashi, F. (2020) · Molecular Cell · Cited by 10 · see citing works

Flagged first, then by citations

2 of the 109 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Boettiger AN 2021 How subtle changes in 3D structure can create large changes in transcription Software Heritage swh:1:rev:8af1e7fcf1fa126908465558c4ef6d127000a9c8 https://archive.softwareheritage.org/swh:1:rev:8af1e7fcf1fa126908465558c4ef6d127000a9c8 PMC8352591 34240703

Sorted by citations

SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks
Bravo González-Blas, C., De Winter, S., Hulselmans, G., Hecker, N., Matetovici, I., Christiaens, V., Poovathingal, S., Wouters, J., Aibar, S., & Aerts, S. (2023) · Nature Methods · doi:10.1038/s41592-023-01938-4 · Cited by 778 · see citing works
Nonlinear control of transcription through enhancer–promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2022) · Nature · doi:10.1038/s41586-022-04570-y · Cited by 415 · see citing works
Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R. (2022) · Nature Genetics · doi:10.1038/s41588-022-01223-8 · Cited by 406 · see citing works
The Mediator complex as a master regulator of transcription by RNA polymerase II
Richter, W. F., Nayak, S., Iwasa, J., & Taatjes, D. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00498-3 · Cited by 312 · see citing works
Deciphering the multi-scale, quantitative cis-regulatory code
Kim, S., & Wysocka, J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.032 · Cited by 282 · see citing works
Topologically associating domain boundaries that are stable across diverse cell types are evolutionarily constrained and enriched for heritability
McArthur, E., & Capra, J. A. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.01.001 · Cited by 200 · see citing works
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
Yang, J. H., & Hansen, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00710-6 · Cited by 191 · see citing works
Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes
Rinzema, N. J., Sofiadis, K., Tjalsma, S. J. D., Verstegen, M. J. A. M., Oz, Y., Valdes-Quezada, C., Felder, A.-K., Filipovska, T., van der Elst, S., de Andrade dos Ramos, Z., et al. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00787-7 · Cited by 166 · see citing works
Topologically associating domain boundaries are required for normal genome function
Rajderkar, S., Barozzi, I., Zhu, Y., Hu, R., Zhang, Y., Li, B., Alcaina‐Caro, A., Fukuda-Yuzawa, Y., Kelman, G., Akeza, A., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04819-w · Cited by 170 · see citing works
The spatial organization of transcriptional control
Hafner, A., & Boettiger, A. N. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00526-0 · Cited by 150 · see citing works
Self-citation
The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communicationPreprint
Karr, J. P., Ferrie, J. J., Tjian, R., & Darzacq, X. (2021) · Genes & Development · doi:10.1101/gad.349160.121 · Cited by 147 · see citing works
The Mediator complex regulates enhancer-promoter interactions
Ramasamy, S., Aljahani, A., Karpińska, M. A., Cao, T. B. N., Velychko, T., Cruz, J., Lidschreiber, M., & Oudelaar, A. M. (2022) · bioRxiv · doi:10.1038/s41594-023-01027-2 · Cited by 104 · see citing works
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF
Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2022) · Nature Communications · doi:10.1038/s41467-022-29696-5 · Cited by 121 · see citing works
Cell-type-specific prediction of 3D chromatin organization enables high-throughput in silico genetic screening
Tan, J., Shenker-Tauris, N., Rodriguez-Hernaez, J., Wang, E., Sakellaropoulos, T., Boccalatte, F. E., Thandapani, P., Skok, J. A., Aifantis, I., Fenyö, D., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01612-8 · Cited by 118 · see citing works
Enhancer-promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness
Chakraborty, S., Kopitchinski, N., Zuo, Z., Eraso, A., Awasthi, P., Chari, R., Mitra, A., Tobias, I. C., Moorthy, S. D., Dale, R. K., et al. (2023) · Nature Genetics · doi:10.1038/s41588-022-01295-6 · Cited by 120 · see citing works
The chromosome folding problem and how cells solve it
Dekker, J., & Mirny, L. A. (2024) · Cell · doi:10.1016/j.cell.2024.10.026 · Cited by 112 · see citing works
New insights into genome folding by loop extrusion from inducible degron technologies
de Wit, E., & Nora, E. P. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00530-4 · Cited by 86 · see citing works
Increased enhancer–promoter interactions during developmental enhancer activation in mammals
Chen, Z., Snetkova, V., Bower, G., Jacinto, S. H., Clock, B., Dizehchi, A., Barozzi, I., Mannion, B. J., Alcaina‐Caro, A., López-Rı́os, J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01681-2 · Cited by 84 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
RNA polymerase II clusters form in line with surface condensation on regulatory chromatin
Pancholi, A., Klingberg, T., Zhang, W., Prizak, R., Mamontova, I., Noa, A., Sobucki, M., Kobitski, A. Y., Nienhaus, G. U., Zaburdaev, V., et al. (2021) · Molecular Systems Biology · doi:10.15252/msb.202110272 · Cited by 83 · see citing works
Functional coordination between transcription factor clustering and gene activity
Kawasaki, K., & Fukaya, T. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.04.018 · Cited by 76 · see citing works
A cohesin traffic pattern genetically linked to gene regulation
Valton, A.-L., Venev, S. V., Mair, B., Khokhar, E. S., Tong, A. H. Y., Ušaj, M., Chan, K., Pai, A. A., Moffat, J., & Dekker, J. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00890-9 · Cited by 77 · see citing works
BRD2 Compartmentalizes the Accessible Genome
Xie, L.-Q., Dong, P., Qi, Y., Hsieh, T.-H. S., English, B. P., Jung, S., Chen, X.-Q., Marzio, M. D., Casellas, R., Chang, H. Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01044-9 · Cited by 52 · see citing works
Nonlinear control of transcription through enhancer-promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2021) · doi:10.1101/2021.04.22.440891 · Cited by 67 · see citing works
Boundary stacking interactions enable cross-TAD enhancer–promoter communication during limb development
Hung, T.-C., Kingsley, D. M., & Boettiger, A. N. (2024) · Nature Genetics · doi:10.1038/s41588-023-01641-2 · Cited by 61 · see citing works
Self-citation
Enhancer-gene specificity in development and disease
Pachano, T., Haro, E., & Rada-Iglesias, Á. (2022) · Development · doi:10.1242/dev.186536 · Cited by 55 · see citing works
Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription
Reed, K. S. M., Davis, E. S., Bond, M. L., Cabrera, A., Thulson, E., Quiroga, I. Y., Cassel, S., Woolery, K. T., Hilton, I. B., Won, H., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111567 · Cited by 54 · see citing works
Enhancer cooperativity can compensate for loss of activity over large genomic distances
Antonović, M., Feng, S., Haslhofer, F., Huber, M., Gallardo, M. G., Loubiere, V., Vanina, D., Pitasi, M., Stark, A., & Buecker, C. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.11.008 · Cited by 50 · see citing works
The stochastic nature of genome organization and function
Sood, V., & Misteli, T. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2021.10.004 · Cited by 56 · see citing works
Genomic environments scale the activities of diverse core promotersPreprint
Hong, C. K., & Cohen, B. A. (2021) · Genome Research · doi:10.1101/gr.276025.121 · Cited by 51 · see citing works
Ultra-long-range interactions between active regulatory elementsPreprint
Friman, E. T., Flyamer, I. M., Marenduzzo, D., Boyle, S., & Bickmore, W. A. (2023) · Genome Research · doi:10.1101/gr.277567.122 · Cited by 49 · see citing works
Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions
Luo, R., Yan, J., Oh, J. W., Wang, X., Shigaki, D., Wong, W., Cho, H., Murphy, D., Cutler, R. R., Rosen, B. P., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01450-7 · Cited by 47 · see citing works
YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle
Lam, J. C., Aboreden, N. G., Midla, S. C., Wang, S., Huang, A., Keller, C. A., Giardine, B. M., Henderson, K. A., Hardison, R. C., Zhang, H., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01871-y · Cited by 45 · see citing works
Genome-wide inference reveals that feedback regulations constrain promoter-dependent transcriptional burst kinetics
Luo, S., Wang, Z., Zhang, Z., Zhou, T., & Zhang, J. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1204 · Cited by 48 · see citing works
Single-molecule states link transcription factor binding to gene expression
Doughty, B. R., Hinks, M. M., Schaepe, J. M., Marinov, G. K., Thurm, A. R., Rios-Martinez, C., Parks, B. E., Tan, Y., Marklund, E., Dubocanin, D., et al. (2024) · Nature · doi:10.1038/s41586-024-08219-w · Cited by 42 · see citing works
Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R. (2021) · doi:10.1101/2021.07.14.452365 · Cited by 42 · see citing works
Size limits the sensitivity of kinetic schemes
Owen, J. A., & Horowitz, J. M. (2023) · Nature Communications · doi:10.1038/s41467-023-36705-8 · Cited by 41 · see citing works
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 40 · see citing works
Long-range regulation of transcription scales with genomic distance in a gene-specific manner
Jensen, C. L., Chen, L.-F., Swigut, T., Crocker, O. J., Yao, D., Bassik, M. C., Ferrell, J. E., Boettiger, A. N., & Wysocka, J. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.10.021 · Cited by 39 · see citing works
Self-citation
Chromatin modules and their implication in genomic organization and gene regulation
van Mierlo, G., Pushkarev, O., Kribelbauer, J. F., & Deplancke, B. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.11.003 · Cited by 32 · see citing works
3D genome folding in epigenetic regulation and cellular memory
Paldi, F., & Cavalli, G. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.03.001 · Cited by 34 · see citing works
Recent progress and challenges in single-cell imaging of enhancer–promoter interaction
Chen, L., Lee, J., & Boettiger, A. N. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102023 · Cited by 29 · see citing works
Self-citation
Uniform dynamics of cohesin-mediated loop extrusion in living human cells
Sabaté, T., Lelandais, B., Robert, M.-C., Szalay, M., Tinevez, J.-Y., Bertrand, E., & Zimmer, C. (2025) · Nature Genetics · doi:10.1038/s41588-025-02406-9 · Cited by 32 · see citing works
Cohesin organizes 3D DNA contacts surrounding active enhancers in C. elegansPreprint
Kim, J., Wang, H., & Ercan, S. (2025) · Genome Research · doi:10.1101/gr.279365.124 · Cited by 31 · see citing works
CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation
Karpińska, M. A., Zhu, Y., Ghazvini, Z. F., Ramasamy, S., Barbieri, M., Cao, T. B. N., Varahram, N., Aljahani, A., Lidschreiber, M., Papantonis, A., et al. (2025) · bioRxiv · doi:10.1038/s41594-025-01555-z · Cited by 28 · see citing works
Complex small-world regulatory networks emerge from the 3D organisation of the human genome
Brackley, C. A., Gilbert, N., Michieletto, D., Papantonis, A., Pereira, M. C. F., Cook, P. R., & Marenduzzo, D. (2021) · Nature Communications · doi:10.1038/s41467-021-25875-y · Cited by 36 · see citing works
Regulatory landscape of enhancer-mediated transcriptional activation
Kawasaki, K., & Fukaya, T. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.01.008 · Cited by 29 · see citing works
Evolution 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 30 · see citing works
What is an enhancer?
Thomas, H., & Buecker, C. (2023) · BioEssays · doi:10.1002/bies.202300044 · Cited by 27 · see citing works
Contributions of 3D chromatin structure to cell-type-specific gene regulation
Schaeffer, M., & Nöllmann, M. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102032 · Cited by 26 · see citing works
RETRACTED: Kinetic organization of the genome revealed by ultraresolution multiscale live imaging
Lee, J., Chen, L., Gaudin, S., Gupta, K., Novačić, A., Spakowitz, A. J., & Boettiger, A. N. (2025) · Science · doi:10.1126/science.adx2202 · Cited by 25 · see citing works
Self-citation
Retracted
Managing the Steady State Chromatin Landscape by Nucleosome Dynamics
Ahmad, K., Henikoff, S., & Ramachandran, S. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104508 · Cited by 25 · see citing works
Dynamic interplay between non-coding enhancer transcription and gene activity in development
Hamamoto, K., Umemura, Y., Makino, S., & Fukaya, T. (2023) · Nature Communications · doi:10.1038/s41467-023-36485-1 · Cited by 24 · see citing works
Power-law behavior of transcriptional bursting regulated by enhancer–promoter communicationPreprint
Wang, Z., Zhang, Z., Luo, S., Zhou, T., & Zhang, J. (2024) · Genome Research · doi:10.1101/gr.278631.123 · Cited by 28 · see citing works
Genome-wide absolute quantification of chromatin looping
Jusuf, J. M., Yang, J. H., Toppen, J., Grosse-Holz, S., Gabriele, M., Mach, P., Flyamer, I. M., Zechner, C., Giorgetti, L., Mirny, L. A., et al. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-026-01819-2 · Cited by 22 · see citing works
“Thus, the probability of loop formation represents an important bio-physical quantity, which can be used to inform quantitative models of chromatin looping and its downstream effects 28–35 .”
4D nucleome equation predicts gene expression controlled by long-range enhancer-promoter interaction
Wang, Z.-H., Luo, S.-H., Zhang, Z.-Q., Zhou, T.-S., & Zhang, J. (2023) · PLoS Comput. Biol. · doi:10.1371/journal.pcbi.1011722 · Cited by 12 · see citing works
Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition
Ealo, T., Sánchez-Gaya, V., Respuela, P., Martín, M. M., Martín-Batista, E., Haro, E., & Rada-Iglesias, Á. (2024) · Nature Communications · doi:10.1038/s41467-024-51602-4 · Cited by 22 · see citing works
Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding
Paldi, F., Szalay, M.-F., Dufau, S., Di Stefano, M., Reboul, H., Jost, D., Bantignies, F., & Cavalli, G. (2026) · Nature Genetics · doi:10.1038/s41588-025-02489-4 · Cited by 18 · see citing works
Emerging insights into enhancer biology and function
Arnold, M., & Stengel, K. R. (2023) · Transcription · doi:10.1080/21541264.2023.2222032 · Cited by 18 · see citing works
Mechanisms of Enhancer-Mediated Gene Activation in the Context of the 3D Genome
Papantonis, A., & Oudelaar, A. M. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120423-012301 · Cited by 18 · see citing works
Enhancer-Promoter Communication: It’s Not Just About Contact
Wurmser, A., & Basu, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.867303 · Cited by 17 · see citing works
Spandrels of the cell nucleus
Solovei, I. V., & Mirny, L. A. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102421 · Cited by 16 · see citing works
Single-molecule chromatin configurations link transcription factor binding to expression in human cellsPreprint
Doughty, B. R., Hinks, M. M., Schaepe, J. M., Marinov, G., Thurm, A. R., Rios-Martinez, C., Parks, B. E., Tan, Y.-X., Marklund, E., Dubocanin, D., et al. (2024) · bioRxiv · doi:10.1101/2024.02.02.578660 · Cited by 14 · see citing works
Understanding transcription across scales: From base pairs to chromosomes
Vos, S. M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.002 · Cited by 16 · see citing works
Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila
Götz, M., Messina, O., Espinola, S., Fiche, J., & Nollmann, M. (2022) · Nature Communications · doi:10.1038/s41467-022-32973-y · Cited by 14 · see citing works
A Cohesin Traffic Pattern Genetically Linked to Gene Regulation
Valton, A.-L., Dekker, J., Venev, S. V., Mair, B., Khokhar, E. S., Pai, A. A., & Moffat, J. (2021) · HAL · Cited by 18 · see citing works
Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions
Wang, R., Xu, Q.-Q., Wang, C., Tian, K., Wang, H., & Ji, X. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad401 · Cited by 14 · see citing works
A cohesin traffic pattern genetically linked to gene regulationPreprint
Valton, A.-L., Venev, S. V., Mair, B., Khokhar, E. S., Tong, A. H. Y., Ušaj, M., Chan, K. S. K., Pai, A. A., Moffat, J., & Dekker, J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.29.454218 · Cited by 13 · see citing works
Polymer simulations guide the detection and quantification of chromatin loop extrusion by imaging
Sabaté, T., Lelandais, B., Bertrand, E., & Zimmer, C. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad034 · Cited by 13 · see citing works
Deep-learning microscopy image reconstruction with quality control reveals second-scale rearrangements in RNA polymerase II clusters
Hajiabadi, H., Mamontova, I., Prizak, R., Pancholi, A., Koziolek, A., & Hilbert, L. (2022) · PNAS Nexus · doi:10.1093/pnasnexus/pgac065 · Cited by 15 · see citing works
Hi-C, a chromatin 3D structure technique advancing the functional genomics of immune cells
Liu, R., Xu, R., Yan, S., Li, P., Jia, C., Sun, H., Sheng, K., Wang, Y., Zhang, Q., Guo, J., et al. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1377238 · Cited by 13 · see citing works
Making connections: enhancers in cellular differentiation
Herrmann, J. C., Beagrie, R. A., & Hughes, J. R. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.10.008 · Cited by 13 · see citing works
The Method in the Madness: transcriptional control from stochastic action at the single-molecule scale
Whitney, P. H., & Lionnet, T. (2024) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102873 · Cited by 10 · see citing works
Cohesin as an essential disruptor of chromosome organization
Bird, A. P. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.01.010 · Cited by 13 · see citing works
De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion
Aboreden, N. G., Zhao, H., Yang, J., Shan, F., Liu, F., Hansen, A. S., Zhang, H., & Blobel, G. A. (2026) · Nature Genetics · doi:10.1038/s41588-026-02565-3 · Cited by 19 · see citing works
The Drosophila embryo as a tabula rasa for the epigenome
Ahmad, K., & Henikoff, S. (2022) · Faculty Reviews · doi:10.12703/r/11-40 · Cited by 9 · see citing works
LAST-seq: single-cell RNA sequencing by direct amplification of single-stranded RNA without prior reverse transcription and second-strand synthesis
Lyu, J., & Chen, C. (2023) · Genome biology · doi:10.1186/s13059-023-03025-5 · Cited by 10 · see citing works
Multiscale Bayesian simulations reveal functional chromatin condensation of gene loci
Brandani, G. B., Gu, C., Gopi, S., & Takada, S. (2024) · PNAS Nexus · doi:10.1093/pnasnexus/pgae226 · Cited by 10 · see citing works
Image-based 3D genomics through chromatin tracing
Yang, T., & Wang, S. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00354-y · Cited by 10 · see citing works
Integrative approaches to study enhancer–promoter communication
Mach, P., & Giorgetti, L. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102052 · Cited by 10 · see citing works
Better together: how cooperativity influences transcriptional bursting.
Fountas, C., & Lenstra, T. (2024) · Current Opinion in Genetics and Development · doi:10.1016/j.gde.2024.102274 · Cited by 4 · see citing works
The Dance of Promoters and Enhancers in Gene Regulation: Fast or Slow, Entwined or Distant?
Nazarova, M., & Sexton, T. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169223 · Cited by 9 · see citing works
Omics Analyses Uncover Host Networks Defining Virus-Permissive and -Hostile Cellular States
Chen, H., Charles, P. D., Gu, Q., Liberatori, S., Robertson, D. L., Palmarini, M., Wilson, S. J., Mohammed, S., & Castelló, A. (2025) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2025.100966 · Cited by 8 · see citing works
Redefining enhancer action: Insights from structural, genomic, and single-molecule perspectives
Llères, D., Gizzi, A. M. C., & Nöllmann, M. (2025) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2025.102527 · Cited by 8 · see citing works
RNA gradients can guide condensates toward promoters: Implications for enhancer–promoter contacts and condensate-promoter kissing
Goh, D., Kannan, D., Natarajan, P., Goychuk, A., & Chakraborty, A. K. (2025) · The Journal of Chemical Physics · doi:10.1063/5.0277838 · Cited by 8 · see citing works
Genome-wide tracing to decipher nuclear organization
Flores, V., Farabella, I., & Nir, G. (2023) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2023.102175 · Cited by 9 · see citing works
Building regulatory landscapes: enhancer recruits cohesin to create contact domains, engage CTCF sites and activate distant genes
Rinzema, N. J., Sofiadis, K., Tjalsma, S. J. D., Verstegen, M. J. A. M., Oz, Y., Valdes-Quezada, C., Felder, A.-K., Filipovska, T., van der Elst, S., de Andrade dos Ramos, Z., et al. (2021) · doi:10.1101/2021.10.05.463209 · Cited by 8 · see citing works
Cross-Species BAC Transgenesis Reveals Long-Range Regulation Drives Variation in Brain Oxytocin Receptor Expression and Social BehaviorsPreprint
Tsukamoto, M., Nagai, L. A., Inoue, K., Kandasamy, L. C., Pires, M. F., Shin, M., Nagasawa, Y., Sambuu, T., Nakai, K., Itohara, S., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.01.518660 · Cited by 8 · see citing works
Kinetic organization of the genome revealed by ultra-resolution, multiscale live imagingPreprint
Lee, J., Chen, L., Gaudin, S., Gupta, K., Spakowitz, A. J., & Boettiger, A. N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.27.645817 · Cited by 8 · see citing works
Self-citation
Enhancer control of promoter activity and variability via frequency modulation of clustered transcriptional burstsPreprint
Tünnermann, J., Roth, G., Cramard, J., & Giorgetti, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.26.645410 · Cited by 8 · see citing works
Loop extrusion creates rare, long-lived encounters underlying enhancer-promoter communicationPreprint
Ubertini, M. A., Louafi, N., Landry, K., Kos, P. I., Roth, G., Marchi, E., Cramard, J., Tiana, G., & Giorgetti, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.24.678119 · Cited by 8 · see citing works
Enhancer cooperativity in the folded genome
Friman, E. T., & Bickmore, W. A. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2025.102416 · Cited by 7 · see citing works
Exploring the interplay between enhancer–promoter interactions and transcription
Kittle, R., & Levo, M. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102303 · Cited by 7 · see citing works
Connecting Chromatin Structures to Gene Regulation Using Dynamic Polymer SimulationsPreprint
Fu, Y., Zhao, T., Clark, F., Nomikou, S., Tsirigos, A., & Lionnet, T. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.07.566032 · Cited by 7 · see citing works
Predicting gene expression changes from chromatin structure modification
Senapati, S., Irshad, I. U., Sharma, A. K., & Kumar, H. (2025) · npj Systems Biology and Applications · doi:10.1038/s41540-025-00510-4 · Cited by 6 · see citing works
A Unified-Field Theory of Genome Organization and Gene Regulation
Negro, G., Semeraro, M., Cook, P. R., & Marenduzzo, D. (2022) · iScience · doi:10.1016/j.isci.2024.111218 · Cited by 7 · see citing works
Nanoscale dynamics of enhancer–promoter interactions during exit from pluripotency
Stumberger, G., Hörl, D., Tsouraki, D., Steinek, C., Oudelaar, A. M., Leonhardt, H., & Harz, H. (2025) · bioRxiv · doi:10.1093/nar/gkaf1255 · Cited by 3 · see citing works
Organization of transcription and 3D genome as revealed by live-cell imaging
Ochiai, H., Ohishi, H., Sato, Y., & Kimurâ, H. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102615 · Cited by 6 · see citing works
A Scaffolding Element Rewires Local 3D Chromatin Architecture During DifferentiationPreprint
Jerković, I., Stefano, M. D., Reboul, H., Szalay, M.-F., Normanno, D., Papadopoulos, G. L., Bantignies, F., & Cavalli, G. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.23.595561 · Cited by 6 · see citing works
Fluctuating Chromatin Facilitates Enhancer–Promoter Communication by Regulating Transcriptional Clustering Dynamics
Zhu, T., Li, C., & Chu, X. (2024) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.4c02453 · Cited by 5 · see citing works

TAD ‐dependent sub‐ TAD is required for enhancer–promoter interaction enabling the β‐globin transcription
Lee, D., Kang, J., & Kim, A. (2024) · The FASEB Journal · doi:10.1096/fj.202401526rr · Cited by 4 · see citing works
TAD boundary architecture and gene activity are uncoupledPreprint
Almansour, F., Fursova, N. A., Keikhosravi, A., Reed, K. S. M., Larson, D. R., Pegoraro, G., & Misteli, T. (2026) · eLife · doi:10.7554/elife.110197.1
Direction and modality of transcription changes caused by TAD boundary disruption in Slc29a3/Unc5b locus depends on tissue-specific epigenetic context
Salnikov, P., Belokopytova, P. S., Yan, A., Viesná, E., Korablev, A. N., Serova, I. A., Lukyanchikova, V., Stepanchuk, Y., Torgunakov, N., Tikhomirov, S., et al. (2025) · Epigenetics & Chromatin · doi:10.1186/s13072-025-00618-1 · Cited by 3 · see citing works
TAD boundaries and gene activity are uncoupledPreprint
Almansour, F., Fursova, N. A., Keikhosravi, A., Reed, K. S. M., Larson, D. R., Pegoraro, G., & Misteli, T. (2026) · eLife · doi:10.7554/elife.110197 · Cited by 2 · see citing works
Selective cross-TAD gene regulation by the Tcra enhancer during T cell developmentPreprint
Rodríguez-Caparrós, A., López-Castellanos, L., López-Ros, J., Castro-Ruiz, V., Duarte-Ruiz, M., Jiménez-Lozano, S., Moreno-Castillo, A., Terron-Camero, L. C., Andrés‐León, E., Suñé, C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.27.721065

Authors: Xiao, J. Y., Hafner, A., & Boettiger, A. N.
Affiliations: Stanford University (US)
Corresponding author: Boettiger, Alistair N
ORCID: Xiao, Jordan Yupeng
Hafner, Antonina
Boettiger, Alistair N
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2021-07-09
Volume: 10
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.64320
PMC: PMC8352591
OpenAlex: W3181995425
Cited by: 162
References: 109
Citations by year: 2026: 18 · 2025: 29 · 2024: 37 · 2023: 36 · 2022: 26 · 2021: 16
FWCI: 9.10
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: eLife (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (U01 DK127419)
NIH (DGM132935A)
Stanford University (GM008294, The Walter V. and Idun Berry Postdoctoral Fellowship Program)
Burroughs Wellcome Fund (CASI)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: topologically associating domains, TAD boundaries, enhancer-promoter interactions, gene expression regulation, bistability, hysteresis, 3D genome organization, stochastic gene expression, promoter activity
MeSH terms: Animals, Chromatin, Gene Expression Regulation, Humans, Hypersensitivity, Promoter Regions, Genetic, Transcription, Genetic, Genome, Computational Biology, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How subtle changes in 3D structure can create large changes in transcription

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks