Loop extrusion explained

Loop extrusion is a major mechanism of Nuclear organization. It is a dynamic process in which structural maintenance of chromosomes (SMC) protein complexes progressively grow loops of DNA or chromatin. In this process, SMC complexes, such as condensin or cohesin, bind to DNA/chromatin, use ATP-driven motor activity to reel in DNA, and as a result, extrude the collected DNA as a loop.

Background

The organization of DNA presents a remarkable biological challenge: human DNA can reach 2 meters^[1] and is packed into the nucleus with the diameter of 5-20 µm.^[2] At the same time, the critical cell processes involve complex processes on highly compacted DNA, such as transcription, replication, recombination, DNA repair, and cell division.

Loop extrusion is a key mechanism that organizes DNA into loops, enabling its efficient compaction and functional organization. For instance, in vitro experiments show that cohesin can compact DNA by 80%,^[3] while condensin achieves a remarkable 10,000-fold compaction of mitotic chromosomes, as evidenced by microscopy, Hi-C, and polymer simulations.^[4]

Another challenge lies in establishing long-range genomic communication, which can span hundreds of thousands of base pairs.^[5] Physical encounters between genomic elements are intrinsically random and promiscuous without mechanisms to facilitate them.^[6] Loop extrusion has been proposed to provide an effective solution to regulate contacts by bringing target elements into proximity while limiting contact with unwanted loci.^[7]

Key components

The key components of the loop extrusion process are

• DNA molecule that serves as the substrate for the movement of extruder
• Extruders, usually SMC complexes, that moves along DNA in ATP-dependent manner
• Accessory factors
  • Loaders of the extruder, a factor that facilitates loading of extruder on DNA (NIPBL/MAU2 usually play the key role in loading extruder on DNA^[8])
  • Unloaders of the extruder, the molecule that facilitates detachment of extruder from DNA (for example, WAPL)
  • Road-blocks located on DNA that present a hindrance to extruder movement and lead to stalling of the extrusion machinery.

SMC proteins

See main article: SMC protein. Loop extrusion is performed by the SMC family of protein-complexes which includes cohesin, condensin, and SMC5/6^[9] each playing specialized roles depending on the organism, cell cycle phase, and biological context. Cohesin mediates chromatin loop formation and stabilization, particularly during interphase in vertebrates, where it facilitates transcriptional regulation by promoting distal enhancer-promoter interactions. During mitosis and meiosis, cohesin dissociates from chromosome arms ceding its loop extrusion role to condensin. Loop extrusion by condensin mediates large-scale chromosome compaction, creating the compact, rod-like chromosome structures required for accurate segregation. Unlike cohesin and condensin, SMC5/6 is a loop extruding factor which primarily functions in maintaining genome integrity during DNA damage repair and resolving replication stress.

Despite their distinct roles, SMC complexes share a highly conserved ring-like structure. Two SMC proteins (usually, SMC1 and SMC3) are connected via a hinge region and linked at their heads by a kleisin subunit, forming a closed ring. These two SMC proteins have ATPase domains at their heads, which bind together and hydrolyze ATP. Cycles of ATP binding and hydrolysis mediate conformational changes in the ring structure, driving DNA translocation and stepwise loop extrusion. ATP is essential for both initiating loop extrusion (e.g., loading SMC complexes onto DNA) and propagating it (growing loops by translocating along DNA). The tension within the DNA significantly influences extrusion efficiency. At low tension, SMC complexes can make larger loop-capture steps, while higher tension can lead to stalling or reversal of loop extrusion.^[10]

Modifications and factors for loading/unloading

The dynamic nature of loop extrusion is tightly controlled by accessory factors and post-translational modifications, especially in the case of cohesin. In vertebrates, NIPBL (and orthologs like Mau2 in yeast or SCC2 and SCC4) is crucial for loading SMC complexes onto DNA, initiating and maintaining active extrusion. PDS5 is thought to pause the extrusion process. The SMC can then either restart extruding or be unloaded by the additional binding of WAPL, which ensure proper recycling and turnover. Post-translational modifications also play a key role. Acetylation of cohesin by enzymes such as ESCO1 and ESCO2 stabilizes chromatin loops, particularly at CTCF-bound sites. Similarly, SUMOylation, mediated by the NSE2 subunit of the SMC5/6 complex, enhances the recruitment of SMC5/6 to sites of DNA damage, supporting its role in genomic stability.

Roadblocks of loop extrusion

Loop extruders can encounter various obstacles while extruding. For example, many of which were shown to directly interact with cohesin and hypothesized to stop its movement on DNA. However, in vivo experiments demonstrate that cohesin can frequently bypass obstacles larger than its ring size.^[11]

1. Other cohesin and condensin molecules: Extruding cohesins and condensins has been found to be obstacle to other extruders that they encounter on the way.^[12] As such, they present a fundamental road-block that can be randomly encountered on the DNA.
2. CTCF: The C-terminal DNA-binding domain of CTCF has been shown to directly interact with SA2 and SCC1 subunits of cohesin to stop extrusion and retain it on DNA^[13] with recent evidence suggesting a tension-dependence to the interaction. CTCF stalls cohesin in a highly directional manner where cohesin can bypass CTCF in one orientation but stalls when encountering it in the opposite orientation.^[14] This directionality allows for the creation of isolated domains on the genome called Topologically Associating Domains (TADs) which have been proposed to have a large role in gene-regulation.^[15]
3. Polymerase: Transcribing polymerases can serve as barriers to cohesin that may not only stall extruders but also act as a motor pushing cohesin in the direction of polymerase movement.^{[16] [17]} The size of a polymerase with an RNA transcript is usually larger than the size of the cohesin ring, and the stall force of cohesin is much smaller than that of polymerase,^[18] allowing for effective barrier function by polymerase. Furthermore, it has been found that RNA can directly interact with cohesin subunits.^[19]
4. Helicase: MCM helicase has been found to counteract the extrusion of cohesin on DNA.^[20]
5. R-loops: Some evidence suggests that R-loops can also act as barriers to loop extrusion,^[21] and R-loops have been shown to interact with cohesin subunits.^[19] However, other evidence suggests that R-loops may instead act as cohesin loaders.^[22]

Molecular mechanism

The molecular mechanisms of DNA-loop extrusion by SMC proteins have not yet been fully understood, but recent structural studies have made significant progress in developing several working models, like the scrunching model,^[23] the Brownian-ratchet model, the DNA-segment capture model/DNA-pumping model, the hold-and-feed model and the swing-and-clamp model.^[24]

Evidence for loop extrusion

Evidence for loop extruding molecules and their properties

The first direct evidence of loop extrusion came from in vitro imaging studies on fluorescently labeled DNA with condensin^[25] or cohesin.^[26] Extrusion was found to be ATP-dependent and happened at ~1-3kb/s. The stall force was measured to be around 0.1-1pN^[27] which is small compared to other molecular motors.^[28]

Evidence for the biological role of loop extrusion

Most work on the biological role of loop extrusion relies on inhibiting loop extruders and observing the consequences. Depletion of cohesin leads to the disappearance of TADs and some loss in transcription genome-wide.^{[29] [30]} In more specific settings, inhibition of cohesin has been found to inhibit neuronal maturation^[31] and differentiation and function of dendritic cells. Depletion of either condensin I or condensin II at the entry into mitosis leads to abnormal chromosome formation and improper segregation of sister chromatids.

Biological function

Loop extrusion has been found across the tree of life with suggested roles in immune response, DNA repair, enhancer-promoter interactions, and mitosis.

• Mitosis in eukaryotes: In mitosis, loop extrusion by condensin is critical for the segregation of sister chromatids and for providing structural rigidity after separation. Condensin I has been found to modulate the size and arrangement of nested inner loops and condensin II organizing the backbone from which loops emanate.
• Cell division in bacteria: In bacteria, SMC proteins have been found to maintain the juxtaposition of the chromosome arms by loading at the centromere and extruding until the terminus.^[32]
• Topologically associating domains (TADs): During interphase, chromosomes are locally compacted at the sub-megabase scale into so-called TADs. Generally, they are bordered by motifs for CTCF and completely disappear if either cohesin or CTCF is degraded.^[33]  
• V(D)J recombination: Loop extrusion by cohesin has been found to play a key role in V(D)J recombination to generate diversity in antibodies and T-cell receptors^{[34] [35]} as depletion of cohesin inhibits V(D)J recombination.^[36] There are CTCF motifs throughout the recombination region, and inversions of their orientation or mutation of the motifs lead to changes in recombination probabilities consistent with those predicted by loop extrusion.^{[37] [38]}
• Protocadherin promoter choice: Protocadherins are mammalian proteins involved in cell adhesion of the neurons encoded in DNA in multiple similar genes located in the protocadherin locus. Neurons usually express only a subset of the protocadherins, enabling variability in the interactions between neurons.^[39] The choice of protocadherins rely on cohesin, which bridges alternative promoters of protocadherin with the enhancer in a CTCF-dependent manner.^[40] This process involves intricate regulation by CTCF^[41] and WAPL.^[42]

Theoretical models of loop extrusion

In mathematical models of loop extrusion, the two legs of a loop-extruding factor (LEF) are represented as points on a one-dimensional line, evolving according to different extrusion policies:

• LEF Translocation : These dictate how LEFs move along the chromatin. These include symmetric extrusion—where both legs move in opposite directions—and one-sided extrusion—where one leg remains stalled while the other moves. Cohesin is often modeled with symmetric extrusion, while condensin is thought to follow a one-sided extrusion mechanism.^[43]
• Stochastic Binding and Unbinding: LEFs bind to chromatin at a random time and position along the chain, and unbind after a characteristic time.
• LEF-LEF interactions: When LEFs encounter one another, different interaction policies can be implemented. LEFs may halt upon collision, or bypass each other, as observed in some contexts.
• Extrusion Barriers: Bound proteins such as CTCF or RNA polymerase II can act as obstacles, stalling or halting LEF motion.

Since the exact modalities of LEF dynamics remain uncertain, these models provide a flexible framework to explore different hypothetical behaviors of LEFs.

In these models, the statistics of LEFs are characterized by two key physical parameters:

• Processivity ($\backslash lambda\; =\; 2v\backslash tau$): Average size of a loop extruded by an unobstructed LEF before dissociating. This characteristic loop size depends on the extrusion speed

v and the residence time \tau of the LEF on the chromatin.

• Separation (

d = L / N ): Average distance between LEFs on the chromatin fiber. It is determined by the total number of LEFs N and the length of the chromatin L . A shorter separation results in denser packing of loops, while larger separation leaves gaps between loops.

The interplay of these two parameters, encapsulated by the dimensionless parameter

λ /d , defines two states of chromatin organization:

• Sparse State (

λ /d \ll 1 ): LEFs operate independently, forming isolated loops with large gaps between them. This state results in minimal compaction of the chromatin fiber.

• Dense State (

λ /d \gg 1 ): LEFs are abundant enough to form a continuous, gapless array of loops. This leads to significant chromatin compaction, as seen during mitosis.

Notes and References

1. Piovesan . Allison . Pelleri . Maria Chiara . Antonaros . Francesca . Strippoli . Pierluigi . Caracausi . Maria . Vitale . Lorenza . 2019-02-27 . On the length, weight and GC content of the human genome . BMC Research Notes . 12 . 1 . 106 . 10.1186/s13104-019-4137-z . free . 30813969 . 6391780 . 1756-0500 .
2. Book: Comprehensive Physiology . 2011-01-31 . Wiley . 978-0-470-65071-4 . Prakash . Y. S. . 1 . en . 10.1002/cphy.c100038 . 4600468 . 23737203 . Lammerding . J. . 1 . 2 . 783–807 .
3. Kim . Yoori . Shi . Zhubing . Zhang . Hongshan . Finkelstein . Ilya J. . Yu . Hongtao . 2019-12-13 . Human cohesin compacts DNA by loop extrusion . Science . 366 . 6471 . 1345–1349 . 10.1126/science.aaz4475 . 31780627 . 7387118 . 2019Sci...366.1345K .
4. Gibcus . Johan H. . Samejima . Kumiko . Goloborodko . Anton . Samejima . Itaru . Naumova . Natalia . Nuebler . Johannes . Kanemaki . Masato T. . Xie . Linfeng . Paulson . James R. . Earnshaw . William C. . Mirny . Leonid A. . Dekker . Job . 2018-02-09 . A pathway for mitotic chromosome formation . Science . 359 . 6376 . –6135 . 10.1126/science.aao6135 . 29348367 . 5924687 .
5. Lancho . Olga . Herranz . Daniel . December 2018 . The MYC Enhancer-ome: Long-Range Transcriptional Regulation of MYC in Cancer . Trends in Cancer . 4 . 12 . 810–822 . 10.1016/j.trecan.2018.10.003 . 2405-8033 . 6260942 . 30470303.
6. Yang . Jin H. . Hansen . Anders S. . July 2024 . Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation . Nature Reviews Molecular Cell Biology . en . 25 . 7 . 574–591 . 10.1038/s41580-024-00710-6 . 1471-0080 . 11574175 . 38413840.
7. Karpinska . Magdalena A . Oudelaar . Aukje Marieke . 2023-04-01 . The role of loop extrusion in enhancer-mediated gene activation . Current Opinion in Genetics & Development . 79 . 102022 . 10.1016/j.gde.2023.102022 . 36842325 . 0959-437X . free .
8. Alonso-Gil . Dácil . Losada . Ana . October 2023 . NIPBL and cohesin: new take on a classic tale . Trends in Cell Biology . en . 33 . 10 . 860–871 . 10.1016/j.tcb.2023.03.006. 37062615 . free .
9. Pradhan . Biswajit . Kanno . Takaharu . Umeda Igarashi . Miki . Loke . Mun Siong . Baaske . Martin Dieter . Wong . Jan Siu Kei . Jeppsson . Kristian . Björkegren . Camilla . Kim . Eugene . April 2023 . The Smc5/6 complex is a DNA loop-extruding motor . Nature . en . 616 . 7958 . 843–848 . 10.1038/s41586-023-05963-3 . 1476-4687 . 10132971 . 37076626. 2023Natur.616..843P .
10. Nomidis . Stefanos K . Carlon . Enrico . Gruber . Stephan . Marko . John F . 2022-05-20 . DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations . Nucleic Acids Research . 50 . 9 . 4974–4987 . 10.1093/nar/gkac268 . 35474142 . 9122525 . 0305-1048 . 2024-11-26.
11. Pradhan . Biswajit . Barth . Roman . Kim . Eugene . Davidson . Iain F. . Bauer . Benedikt . van Laar . Theo . Yang . Wayne . Ryu . Je-Kyung . van der Torre . Jaco . Peters . Jan-Michael . Dekker . Cees . 2022-10-18 . SMC complexes can traverse physical roadblocks bigger than their ring size . Cell Reports . 41 . 3 . 111491 . 10.1016/j.celrep.2022.111491 . 36261017 . 2211-1247.
12. Goloborodko . Anton . Marko . John F. . Mirny . Leonid A. . 2016-05-24 . Chromosome Compaction by Active Loop Extrusion . Biophysical Journal . 110 . 10 . 2162–2168 . 10.1016/j.bpj.2016.02.041 . 27224481 . 4880799 . 2016BpJ...110.2162G . 0006-3495 .
13. Li . Yan . Haarhuis . Judith H. I. . Sedeño Cacciatore . Ángela . Oldenkamp . Roel . van Ruiten . Marjon S. . Willems . Laureen . Teunissen . Hans . Muir . Kyle W. . de Wit . Elzo . Rowland . Benjamin D. . Panne . Daniel . February 2020 . The structural basis for cohesin–CTCF-anchored loops . Nature . en . 578 . 7795 . 472–476 . 10.1038/s41586-019-1910-z . 31905366 . 7035113 . 2020Natur.578..472L . 1476-4687.
14. de Wit . Elzo . Vos . Erica S. M. . Holwerda . Sjoerd J. B. . Valdes-Quezada . Christian . Verstegen . Marjon J. A. M. . Teunissen . Hans . Splinter . Erik . Wijchers . Patrick J. . Krijger . Peter H. L. . de Laat . Wouter . 2015-11-19 . CTCF Binding Polarity Determines Chromatin Looping . Molecular Cell . 60 . 4 . 676–684 . 10.1016/j.molcel.2015.09.023 . 26527277 . 1097-2765.
15. Lupiáñez . Darío G. . Kraft . Katerina . Heinrich . Verena . Krawitz . Peter . Brancati . Francesco . Klopocki . Eva . Horn . Denise . Kayserili . Hülya . Opitz . John M. . Laxova . Renata . Santos-Simarro . Fernando . Gilbert-Dussardier . Brigitte . Wittler . Lars . Borschiwer . Marina . Haas . Stefan A. . 2015-05-21 . Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions . Cell . 161 . 5 . 1012–1025 . 10.1016/j.cell.2015.04.004 . 0092-8674 . Osterwalder . Marco . Franke . Martin . Timmermann . Bernd . Hecht . Jochen . Spielmann . Malte . Visel . Axel . Mundlos . Stefan. 25959774 . 4791538 .
16. Banigan . Edward J. . Tang . Wen . van den Berg . Aafke A. . Stocsits . Roman R. . Wutz . Gordana . Brandão . Hugo B. . Busslinger . Georg A. . Peters . Jan-Michael . Mirny . Leonid A. . 2023-03-14 . Transcription shapes 3D chromatin organization by interacting with loop extrusion . Proceedings of the National Academy of Sciences of the United States of America . 120 . 11 . e2210480120 . 10.1073/pnas.2210480120 . 1091-6490 . 36897969. 10089175 . 2023PNAS..12010480B .
17. Brandão . Hugo B. . Paul . Payel . van den Berg . Aafke A. . Rudner . David Z. . Wang . Xindan . Mirny . Leonid A. . 2019-10-08 . RNA polymerases as moving barriers to condensin loop extrusion . Proceedings of the National Academy of Sciences of the United States of America . 116 . 41 . 20489–20499 . 10.1073/pnas.1907009116 . free . 1091-6490 . 6789630 . 31548377. 2019PNAS..11620489B .
18. Banigan . Edward J. . Mirny . Leonid A. . 2020-06-01 . Loop extrusion: theory meets single-molecule experiments . Current Opinion in Cell Biology . Cell Nucleus . 64 . 124–138 . 10.1016/j.ceb.2020.04.011 . 32534241 . 0955-0674 . 2022-04-02.
19. Porter . Hayley . Li . Yang . Neguembor . Maria Victoria . Beltran . Manuel . Varsally . Wazeer . Martin . Laura . Cornejo . Manuel Tavares . Pezić . Dubravka . Bhamra . Amandeep . Surinova . Silvia . Jenner . Richard G . Cosma . Maria Pia . Hadjur . Suzana . 2023-04-03 . Aguilera . Andrés . Struhl . Kevin . Vannini . Alessandro . Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading . eLife . 12 . e79386 . 10.7554/eLife.79386 . free . 37010886 . 10238091 . 2050-084X.
20. Dequeker . Bart J. H. . Scherr . Matthias J. . Brandão . Hugo B. . Gassler . Johanna . Powell . Sean . Gaspar . Imre . Flyamer . Ilya M. . Lalic . Aleksandar . Tang . Wen . Stocsits . Roman . Davidson . Iain F. . Peters . Jan-Michael . Duderstadt . Karl E. . Mirny . Leonid A. . Tachibana . Kikuë . June 2022 . MCM complexes are barriers that restrict cohesin-mediated loop extrusion . Nature . en . 606 . 7912 . 197–203 . 10.1038/s41586-022-04730-0 . 35585235 . 9159944 . 2022Natur.606..197D . 1476-4687.
21. Zhang . Hongshan . Shi . Zhubing . Banigan . Edward J. . Kim . Yoori . Yu . Hongtao . Bai . Xiao-chen . Finkelstein . Ilya J. . August 2023 . CTCF and R-loops are boundaries of cohesin-mediated DNA looping . Molecular Cell . en . 83 . 16 . 2856–2871.e8 . 10.1016/j.molcel.2023.07.006. 37536339 .
22. Porter . Hayley . Li . Yang . Neguembor . Maria Victoria . Beltran . Manuel . Varsally . Wazeer . Martin . Laura . Cornejo . Manuel Tavares . Pezić . Dubravka . Bhamra . Amandeep . Surinova . Silvia . Jenner . Richard G . Cosma . Maria Pia . Hadjur . Suzana . 2023-04-03 . Aguilera . Andrés . Struhl . Kevin . Vannini . Alessandro . Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading . eLife . 12 . e79386 . 10.7554/eLife.79386 . free . 2050-084X . 10238091 . 37010886.
23. Ryu . Je-Kyung . Katan . Allard J. . van der Sluis . Eli O. . Wisse . Thomas . de Groot . Ralph . Haering . Christian H. . Dekker . Cees . December 2020 . The condensin holocomplex cycles dynamically between open and collapsed states . Nature Structural & Molecular Biology . en . 27 . 12 . 1134–1141 . 10.1038/s41594-020-0508-3 . 32989304 . 1545-9993.
24. Bauer . Benedikt W. . Davidson . Iain F. . Canena . Daniel . Wutz . Gordana . Tang . Wen . Litos . Gabriele . Horn . Sabrina . Hinterdorfer . Peter . Peters . Jan-Michael . October 2021 . Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism . Cell . 184 . 21 . 5448–5464.e22 . 10.1016/j.cell.2021.09.016 . 0092-8674 . 8563363 . 34624221.
25. Ganji . Mahipal . Shaltiel . Indra A. . Bisht . Shveta . Kim . Eugene . Kalichava . Ana . Haering . Christian H. . Dekker . Cees . 2018-04-06 . Real-time imaging of DNA loop extrusion by condensin . Science . 360 . 6384 . 102–105 . 10.1126/science.aar7831 . 29472443 . 6329450 . 2018Sci...360..102G .
26. Davidson . Iain F. . Bauer . Benedikt . Goetz . Daniela . Tang . Wen . Wutz . Gordana . Peters . Jan-Michael . 2019-12-13 . DNA loop extrusion by human cohesin . Science . 366 . 6471 . 1338–1345 . 10.1126/science.aaz3418 . 31753851 . 2019Sci...366.1338D . 2022-06-15.
27. Golfier . S. . Quail . T. . Kimura . H. . Brugués . J. . 2020 . Cohesin and condensin extrude DNA loops in a cell-cycle dependent manner . eLife . 9 . 1–34 . 10.7554/eLife.53885 . free . 32396063 . 7316503 . 2050-084X.
28. Mallik . Roop . Gross . Steven P. . November 2004 . Molecular Motors: Strategies to Get Along . Current Biology . en . 14 . 22 . R971–R982 . 10.1016/j.cub.2004.10.046. 15556858 . 2004CBio...14.R971M .
29. Rao . Suhas S. P. . Huang . Su-Chen . Glenn St Hilaire . Brian . Engreitz . Jesse M. . Perez . Elizabeth M. . Kieffer-Kwon . Kyong-Rim . Sanborn . Adrian L. . Johnstone . Sarah E. . Bascom . Gavin D. . Bochkov . Ivan D. . Huang . Xingfan . Shamim . Muhammad S. . Shin . Jaeweon . Turner . Douglass . Ye . Ziyi . 2017-10-05 . Cohesin Loss Eliminates All Loop Domains . Cell . 171 . 2 . 305–320.e24 . 10.1016/j.cell.2017.09.026 . 0092-8674 . Omer . Arina D. . Robinson . James T. . Schlick . Tamar . Bernstein . Bradley E. . Casellas . Rafael . Lander . Eric S. . Aiden . Erez Lieberman. 28985562 . 5846482 .
30. Schwarzer . Wibke . Abdennur . Nezar . Goloborodko . Anton . Pekowska . Aleksandra . Fudenberg . Geoffrey . Loe-Mie . Yann . Fonseca . Nuno A. . Huber . Wolfgang . Haering . Christian H. . Mirny . Leonid . Spitz . Francois . 2017-11-02 . Two independent modes of chromatin organization revealed by cohesin removal. . Nature . 551 . 7678 . 51–56 . 2017Natur.551...51S . 10.1038/nature24281 . 1476-4687 . 5687303 . 29094699.
31. Calderon . Lesly . Weiss . Felix D . Beagan . Jonathan A . Oliveira . Marta S . Georgieva . Radina . Wang . Yi-Fang . Carroll . Thomas S . Dharmalingam . Gopuraja . Gong . Wanfeng . Tossell . Kyoko . de Paola . Vincenzo . Whilding . Chad . Ungless . Mark A . Fisher . Amanda G . Phillips-Cremins . Jennifer E . 2022-04-26 . Day . Jeremy J . Struhl . Kevin . Cohesin-dependence of neuronal gene expression relates to chromatin loop length . eLife . 11 . e76539 . 10.7554/eLife.76539 . free . 2050-084X . 9106336 . 35471149.
32. Wang . Xindan . Brandão . Hugo B. . Le . Tung B. K. . Laub . Michael T. . Rudner . David Z. . 2017-02-03 . Bacillus subtilis SMC complexes juxtapose chromosome arms as they travel from origin to terminus . Science . 355 . 6324 . 524–527 . 10.1126/science.aai8982 . 28154080 . 5484144 . 2017Sci...355..524W .
33. Rao . Suhas S.P. . Huntley . Miriam H. . Durand . Neva C. . Stamenova . Elena K. . Bochkov . Ivan D. . Robinson . James T. . Sanborn . Adrian L. . Machol . Ido . Omer . Arina D. . Lander . Eric S. . Aiden . Erez Lieberman . December 2014 . A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping . Cell . en . 159 . 7 . 1665–1680 . 10.1016/j.cell.2014.11.021 . 5635824 . 25497547.
34. Peters . Jan-Michael . 2021-06-01 . How DNA loop extrusion mediated by cohesin enables V(D)J recombination . Current Opinion in Cell Biology . Cell Nucleus . 70 . 75–83 . 10.1016/j.ceb.2020.11.007 . 33422934 . 0955-0674. free .
35. Zhang . Yu . Zhang . Xuefei . Dai . Hai-Qiang . Hu . Hongli . Alt . Frederick W. . September 2022 . The role of chromatin loop extrusion in antibody diversification . Nature Reviews Immunology . en . 22 . 9 . 550–566 . 10.1038/s41577-022-00679-3 . 1474-1741 . 9376198 . 35169260.
36. Ba . Zhaoqing . Lou . Jiangman . Ye . Adam Yongxin . Dai . Hai-Qiang . Dring . Edward W. . Lin . Sherry G. . Jain . Suvi . Kyritsis . Nia . Kieffer-Kwon . Kyong-Rim . Casellas . Rafael . Alt . Frederick W. . October 2020 . CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning . Nature . en . 586 . 7828 . 305–310 . 10.1038/s41586-020-2578-0 . 1476-4687 . 7554077 . 32717742. 2020Natur.586..305B .
37. Dai . Hai-Qiang . Hu . Hongli . Lou . Jiangman . Ye . Adam Yongxin . Ba . Zhaoqing . Zhang . Xuefei . Zhang . Yiwen . Zhao . Lijuan . Yoon . Hye Suk . Chapdelaine-Williams . Aimee M. . Kyritsis . Nia . Chen . Huan . Johnson . Kerstin . Lin . Sherry . Conte . Andrea . February 2021 . Loop extrusion mediates physiological Igh locus contraction for RAG scanning . Nature . en . 590 . 7845 . 338–343 . 10.1038/s41586-020-03121-7 . 1476-4687 . 9037962 . 33442057. 2021Natur.590..338D .
38. Zhang . Yu . Zhang . Xuefei . Ba . Zhaoqing . Liang . Zhuoyi . Dring . Edward W. . Hu . Hongli . Lou . Jiangman . Kyritsis . Nia . Zurita . Jeffrey . Shamim . Muhammad S. . Presser Aiden . Aviva . Lieberman Aiden . Erez . Alt . Frederick W. . September 2019 . The fundamental role of chromatin loop extrusion in physiological V(D)J recombination . Nature . en . 573 . 7775 . 600–604 . 10.1038/s41586-019-1547-y . 1476-4687 . 6867615 . 31511698. 2019Natur.573..600Z .
39. Tasic . Bosiljka . Nabholz . Christoph E. . Baldwin . Kristin K. . Kim . Youngwook . Rueckert . Erroll H. . Ribich . Scott A. . Cramer . Paula . Wu . Qiang . Axel . Richard . Maniatis . Tom . July 2002 . Promoter Choice Determines Splice Site Selection in Protocadherin α and γ Pre-mRNA Splicing . Molecular Cell . en . 10 . 1 . 21–33 . 10.1016/S1097-2765(02)00578-6. 12150904 .
40. Monahan . Kevin . Rudnick . Noam D. . Kehayova . Polina D. . Pauli . Florencia . Newberry . Kimberly M. . Myers . Richard M. . Maniatis . Tom . 2012-06-05 . Role of CCCTC binding factor (CTCF) and cohesin in the generation of single-cell diversity of Protocadherin-α gene expression . Proceedings of the National Academy of Sciences . en . 109 . 23 . 9125–9130 . 10.1073/pnas.1205074109 . free . 0027-8424 . 3384188 . 22550178. 2012PNAS..109.9125M .
41. Guo . Ya . Monahan . Kevin . Wu . Haiyang . Gertz . Jason . Varley . Katherine E. . Li . Wei . Myers . Richard M. . Maniatis . Tom . Wu . Qiang . 2012-12-18 . CTCF/cohesin-mediated DNA looping is required for protocadherin α promoter choice . Proceedings of the National Academy of Sciences . en . 109 . 51 . 21081–21086 . 10.1073/pnas.1219280110 . free . 0027-8424 . 3529044 . 23204437. 2012PNAS..10921081G .
42. Kiefer . Lea . Chiosso . Anna . Langen . Jennifer . Buckley . Alex . Gaudin . Simon . Rajkumar . Sandy M. . Servito . Gabrielle Isabelle F. . Cha . Elizabeth S. . Vijay . Akshara . Yeung . Albert . Horta . Adan . Mui . Michael H. . Canzio . Daniele . 2023-06-23 . WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring . Science . en . 380 . 6651 . eadf8440 . 10.1126/science.adf8440 . 37347873 . 0036-8075.
43. Banigan . Edward J . van den Berg . Aafke A . Brandão . Hugo B . Marko . John F . Mirny . Leonid A . 2020-04-06 . Chromosome organization by one-sided and two-sided loop extrusion . eLife . en . 9 . 10.7554/eLife.53558 . 2050-084X . 7295573 . 32250245 . free.