chromosome condensation

A diploid human cell contains 46 chromosomes: 22 pairs of autosomes (22 × 2) and one pair of sex chromosomes (XX or XY). The total length of DNA within a single nucleus reaches ~2 m. These DNA molecules are initially wrapped around histones to form nucleosomes, which are further compacted into chromatin fibers, commonly referred to as 30-nm fibers. During interphase, these fibers are confined within the nucleus, which has a diameter of only ~10–20 um. During mitosis, chromatin is reorganized into a set of rod-shaped structures (i.e., mitotic chromosomes) that can be individually distinguished under a microscope.

This transformation was first described meticulously in the late 19th century by the German cytologist Walther Flemming. Originally, the term "chromosome" referred specifically to these highly condensed mitotic structures, although its meaning has since broadened (see chromosome).

In mitotic chromosomes of higher eukaryotes, DNA is compacted lengthwise by a factor of ~10,000. For example, human chromosome 8 contains a DNA molecule about 50 mm long, yet it is folded into a metaphase chromosome only ~5 um in length. This degree of compaction is comparable to folding a 600-meter-long thread (the height of the Tokyo Skytree) into the size of an AA battery.

As described above, although DNA in interphase is already organized into chromatin, it is dispersed throughout the nucleus and therefore not observed as individual chromosomes. Upon entry into prophase, condensation begins near the nuclear periphery, and fibrous structures gradually become visible. After nuclear envelope breakdown in prometaphase, condensation proceeds further. By metaphase, when condensation is apparently complete, the two sister chromatids of each chromosome can be clearly distinguished. This entire sequence of processes is often collectively referred to as chromosome condensation; however, due to our currently limited understanding of the higher-order structure of chromosomes, the precise definition of this term remains ambiguous.

File:Condensation4.png

File:Resolution6E.png

In principle, the process of chromosome condensation can be divided into three sequential but overlapping steps (Figure 2):{{cite journal | author = Hirano T | title = Chromosome shaping by two condensins | journal = Cell Cycle | volume = 3 | pages = 26–28 | year = 2004 | issue = 1 | doi = 10.4161/cc.3.1.633 | pmid = 14657659}}

1. Individualization – Disentanglement of chromatin fibers dispersed throughout the nucleus into discrete chromosome units.

2. Shaping/Compaction – Organization of each chromosome into a compact, rod-like structure.

3. Resolution – Resolution of replicated DNA strands within each chromosome into two distinct sister chromatids.

Although conceptually distinct, these steps occur concurrently and synergistically during mitosis. For this reason, the entire process is often collectively referred to as chromosome condensation.

Importantly, chromosome condensation is not merely a reduction in chromatin length. Rather, it involves the organized folding of chromatin, initially in a random-coil–like state, into a highly structured rod-shaped form. This structural transformation is critical for ensuring the proper separation of sister chromatids during anaphase and provides the mechanical stiffness necessary for their faithful segregation (Figure 3).{{cite journal | author = Hirano T | title = Condensins: organizing and segregating the genome | journal = Curr. Biol. | volume = 15 | pages = R265-275 | year = 2005 | issue = 7 | doi = 10.1016/j.cub.2005.03.037 | pmid = 15823530| bibcode = 2005CBio...15.R265H }} Defects in chromosome condensation can impair chromosome segregation and ultimately lead to genome instability.

Eukaryotic chromosome condensation has long been regarded as a highly complex process involving numerous proteins. However, recent studies have shown that single chromatids can be reconstituted in vitro by mixing sperm nuclei with only six purified proteins: core histones, three histone chaperones, topoisomerase II, and condensin I.{{cite journal | author = Shintomi K, Takahashi TS, Hirano T | title = Reconstitution of mitotic chromatids with a minimum set of purified factors | journal = Nat Cell Biol | volume = 17 | issue = 8 | year = 2015 | pages = 1014–1023 | doi = 10.1038/ncb3187 | pmid = 26075356}}{{cite journal | author = Shintomi K, Hirano T | title = Guiding functions of the C-terminal domain of topoisomerase IIα advance mitotic chromosome assembly | journal = Nat Commun | volume = 12 | issue = 1 | page = 2917 | year = 2021 | doi = 10.1038/s41467-021-23205-w | pmid = 34006877| pmc = 8131626 | bibcode = 2021NatCo..12.2917S }} The three histone chaperones serve distinct roles in this reconstitution assay: (1) Npm2 (Nucleoplasmin 2) removes basic sperm-specific proteins from sperm chromatin; (2) Nap1 (Nucleosome assembly protein 1) deposits core histones H2A-H2B onto DNA to form nucleosomes; (3) FACT (Facilitates Chromatin Transcription) dynamically remodels nucleosomes, thereby aiding the actions of topoisomerase II and condensin I. These chaperones do not remain associated with the final product of mitotic chromatids. In other words, the core reactions of mitotic chromosome condensation can be recapitulated using only three structural proteins, core histones, topoisomerase II, and condensin I, provided that their actions are aided by appropriate chaperone-mediated regulation.

Independent lines of previous evidence support this simple picture of chromosome condensation. For example, it has long been known that histones account for approximately half of the total protein mass in mitotic chromosomes. Both topoisomerase II and condensin I have been identified as major structural components of mitotic chromosomes {{cite journal | author = Hirano T, Mitchison TJ | title = Topoisomerase II does not play a scaffolding role in the organization of mitotic chromosomes assembled in Xenopus egg extracts | journal = J Cell Biol | volume = 120 | issue = 3 | pages = 601–612 | year = 1993 | pmid = 8381118 | doi = 10.1083/jcb.120.3.601| pmc = 2119547 }}{{cite journal | author = Hirano T, Kobayashi R, Hirano M. | title = Condensins, chromosome condensation complex containing XCAP-C, XCAP-E and a Xenopus homolog of the Drosophila Barren protein | journal = Cell | volume = 89 | issue = 4 | pages = 511–21 | year = 1997 | doi = 10.1016/s0092-8674(00)80233-0 | pmid = 9160743}} as well as of the so-called chromosome scaffold.{{cite journal | author = Maeshima K, Laemmli UK | title = A two-step scaffolding model for mitotic chromosome assembly | journal = Dev Cell | volume = 4 | issue = 4 | pages = 467–480 | year = 2003 | pmid = 12689587 | doi = 10.1016/s1534-5807(03)00092-3}} Functional assays using Xenopus egg extracts and genetic analyses in fission yeast {{cite journal | author = Uemura T, Ohkura H, Adachi Y, Morino K, Shiozaki K, Yanagida M | title = DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe | journal = Cell | volume = 50 | issue = 6 | pages = 917–925 | year = 1987 | pmid = 3040264 | doi = 10.1016/0092-8674(87)90518-6}}{{cite journal | author = Saka Y, Sutani T, Yamashita Y, Saitoh S, Takeuchi M, Nakaseko Y, Yanagida M | title = Fission yeast cut3 and cut14, members of a ubiquitous protein family, are required for chromosome condensation and segregation in mitosis | journal = EMBO J | volume = 13 | issue = 20 | pages = 4938–4952 | year = 1994 | pmid = 7957061 | doi = 10.1002/j.1460-2075.1994.tb06821.x| pmc = 395434 }} have demonstrated that both proteins are essential for properly assembling mitotic chromosomes.

Surprisingly, it has been shown that chromosome-like structures can be assembled in Xenopus egg extracts even under conditions in which nucleosome assembly is suppressed, in a manner dependent on condensins and topoisomerase II.Shintomi K, Inoue F, Watanabe H, Ohsumi K, Ohsugi M, Hirano T. (2017). "Mitotic chromosome assembly despite nucleosome depletion in Xenopus egg extracts". Science, 356 (6344):1284-1287. PMID [https://www.ncbi.nlm.nih.gov/pubmed/28522692 28522692] These “nucleosome-depleted" chromosomes consist of a central condensin-enriched axis and extended DNA loops emanating from it. This observation indicates that condensins are essential for the shaping of chromosome architecture, whereas histones contribute to the compaction of DNA loops.

Chromosome condensation is a process unique to mitosis and meiosis, and thus, the proteins involved in this process are subject to cell cycle regulation, often mediated by post-translational modifications (PTMs).

Among these, the most intensively studied mechanism is the phosphorylation of condensin complexes. It has been shown that phosphorylation by Cdk1 is essential for both the DNA supercoiling activity {{cite journal | author = Kimura K, Hirano M, Kobayashi R, Hirano T | title =Phosphorylation and activation of 13S condensin by Cdc2 in vitro | journal = Science| volume = 282 | issue = 5388 | pages = 487–490 | year = 1998 | doi =10.1126/science.282.5388.487 | pmid = 9774278| bibcode =1998Sci...282..487K }} and chromosome assembly activity of condensin I. Experiments using Xenopus egg extracts have led to a proposed mechanism in which phosphorylation of the N-terminal region of the CAP-H subunit relieves its self-suppression, thereby activating condensin I.{{cite journal | author = Tane S, Shintomi K, Kinoshita K, Tsubota Y, Yoshida MM, Nishiyama T, Hirano T | title = Cell cycle-specific loading of condensin I is regulated by the N-terminal tail of its kleisin subunit | journal = eLife| volume = 11 | pages = e84694 | year = 2022 | doi = 10.7554/eLife.84694 | doi-access = free | pmid = 36511239| pmc = 9797191 }} Similarly, in condensin II, Cdk1-dependent phosphorylation of the C-terminal region of the CAP-D3 subunit plays a role in releasing its inhibitory constraint.{{cite journal | author = Yoshida MM, Kinoshita K, Aizawa Y, Tane S, Yamashita D, Shintomi K, Hirano T | title = Molecular dissection of condensin II-mediated chromosome assembly using in vitro assays | journal = eLife | volume = 11 | pages = e78984 | year = 2022 | doi = 10.7554/eLife.78984 | doi-access = free | pmid = 35983835| pmc = 9433093 }}{{cite journal | author = Yoshida MM, Kinoshita K, Shintomi K, Aizawa Y, Hirano T | title = Regulation of condensin II by self-suppression and release mechanisms | journal = Mol Biol Cell | volume = 35 | issue = 2 | pages = ar21 | year = 2024 | doi = 10.1091/mbc.E23-10-0392 | pmid = 38088875| pmc = 10881152 }} However, phosphoregulation of condensins is complex and multilayered, and a full mechanistic understanding has not yet been achieved.

Topoisomerase II is also subject to numerous PTMs. However, it remains unclear whether any of these modifications specifically regulate its activity during mitosis.{{cite journal | author = Dekker B, Dekker J | title = Regulation of the mitotic chromosome folding machines | journal = Biochem J | volume = 479 | issue = 20 | pages = 2153–2173 | year = 2022 | pmid = 36268993 | pmc = 9704520 | doi = 10.1042/BCJ20210140}}{{cite journal | author = Lee JH, Berger JM | title = Cell Cycle-Dependent Control and Roles of DNA Topoisomerase II | journal = Genes (Basel) | volume = 10 | issue = 11 | pages = 859 | year = 2019 | pmid = 31671531 | pmc = 6893486 | doi = 10.3390/genes10110859| doi-access = free }}

Mitotic phosphorylation of linker histone H1 and core histone H3 has been known for decades.{{cite journal | author = Bradbury EM | title = Reversible histone modifications and the chromosome cell cycle | journal = BioEssays | volume = 14 | issue = 1 | pages = 9–16 | year = 1992 | pmid = 1312335 | doi = 10.1002/bies.950140103}} Nevertheless, there is currently no direct evidence that these modifications actively or directly regulate chromosome condensation. In contrast, histone deacetylation has recently been reported to play an important role in this process through a mechanism of phase transition.{{cite journal | author = Schneider MWG, Gibson BA, Otsuka S, Spicer MFD, Petrovic M, Blaukopf C, Langer CCH, Batty P, Nagaraju T, Doolittle LK, Rosen MK, Gerlich DW | title = A mitotic chromatin phase transition prevents perforation by microtubules | journal = Nature | volume = 609 | issue = 7925 | pages = 183–190 | year = 2022 | pmid = 35922507 | pmc = 9433320 | doi = 10.1038/s41586-022-05027-y| bibcode = 2022Natur.609..183S }}

In addition to PTMs, external regulatory factors also contribute to the regulation of chromosome condensation. For example, KIF4A, a chromokinesin, acts as a positive regulator of condensin I,{{cite journal | author = Takahashi M, Wakai T, Hirota T | title = Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A | journal = Genes Dev | volume = 30 | issue = 17 | pages = 1931–1936 | year = 2016 | pmid = 27633014 | doi = 10.1101/gad.282855.116| pmc = 5066236 }}{{cite journal | author = Cutts EE, Tetiker D, Kim E, Aragon L | title = Molecular mechanism of condensin I activation by KIF4A.| journal =EMBO J | year = 2024 | volume = 44| issue = 3| pages = 682–704| doi = 10.1038/s44318-024-00340-w| pmid = 39690239 | pmc = 11790958}} whereas MCPH1, a microcephaly-associated protein, serves as a negative regulator of condensin II.{{cite journal | author = Yamashita D, Shintomi K, Ono T, Gavvovidis I, Schindler D, Neitzel H, Trimborn M, Hirano T| title = MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II| journal = J. Cell Biol.| volume = 194 | issue = 6 | pages = 841–854 | year = 2011 | doi = 10.1083/jcb.201106141| pmid = 21911480| pmc = 3207293}}{{cite journal | author = Houlard M, Cutts EE, Shamim MS, Godwin J, Weisz D, Presser Aiden A, Lieberman Aiden E, Schermelleh L, Vannini A, Nasmyth K | title = MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface | journal = eLife | volume = 10 | pages = 451–469 | year = 2021 | issue = 2 | pmid = 34850993 | doi = 10.7554/eLife.73348| doi-access = free | pmc = 8673838 }} Ki-67, a nucleolar protein, plays a critical role in chromosome individualization during early mitosis by coating the surface of mitotic chromosomes.{{cite journal | author = Cuylen S, Blaukopf C, Politi AZ, Müller-Reichert T, Neumann B, Poser I, Ellenberg J, Hyman AA, Gerlich DW | title = Ki-67 acts as a biological surfactant to disperse mitotic chromosomes | journal = Nature | volume = 535 | issue = 7611 | pages = 308–312 | year = 2016 | pmid = 27362226 | doi = 10.1038/nature18610| pmc = 4947524 | bibcode = 2016Natur.535..308C }}{{cite journal | author = Takagi M, Ono T, Natsume T, Sakamoto C, Nakao M, Saitoh N, Kanemaki MT, Hirano T, Imamoto N | title = Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms | journal = J Cell Sci | volume = 131 | issue = 6 | pages = jcs212092 | year = 2018 | pmid = 29487178 | doi = 10.1242/jcs.212092}}

How chromatin fibers are folded within mitotic chromosomes remains an unsolved question in cell biology. Several models have been proposed to explain the higher-order architecture of condensed chromosomes. Classical models include the hierarchical folding model {{cite journal | author = Sedat J, Manuelidis L| title = A direct approach to the structure of eukaryotic chromosomes| journal = Cold Spring Harb. Symp. Quant. Biol. | volume = 42 | pages = 331–350 | year = 1978 | doi = 10.1101/sqb.1978.042.01.035| pmid = 98280 }} and the radial loop model.{{cite journal | author =Paulson JR, Laemmli UK| title = The structure of histone-depleted metaphase chromosomes | journal = Cell | volume = 12 | pages = 817–828 | year = 1977 | issue = 3 | doi = 10.1016/0092-8674(77)90280-x | pmid = 922894 }} More recently, additional models such as the polymer model {{cite journal | author = Marko JF, Siggia ED| title = Polymer models of meiotic and mitotic chromosomes | journal = Mol. Biol. Cell | volume = 8 | pages = 2217–2231| year = 1997 | issue = 11 | doi = 10.1091/mbc.8.11.2217 | pmid = 9362064| pmc = 25703 }} and the hierarchical folding and axial glue model {{cite journal | author = Kireeva N, Lakonishok M, Kireev I, Hirano T, Belmont AS| title = Visualization of early chromosome condensation: a hierarchical folding, axial glue model of chromosome structure | journal = J. Cell Biol. | volume = 166 | pages = 775–785| year = 2004| issue = 6 | doi = 10.1083/jcb.200406049 | pmid = 15353545| pmc = 2172117 }} have been introduced.

One of the major reasons for the slow progress in understanding the folding of chromatin fibers within mitotic chromosomes has been the limited availability of experimental tools for their structural analysis. Recently, however, the development of a variety of new technologies has enabled more detailed and multifaceted investigations.

• Hi-C (High-throughput chromosome conformation capture)
• Cell cycle–dependent changes in human cultured cells and modeling of mitotic chromosomes as polymers {{cite journal | author = Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, Mirny LA, Dekker J| title = Organization of the mitotic chromosome | journal = Science | volume = 342 | pages = 948–953 | year = 2013 | issue = 6161 | doi = 10.1126/science.1236083 | pmid = 24200812| pmc = 4040465 | bibcode = 2013Sci...342..948N }}
• Comparison of diploid and polytene chromosomes in Drosophila melanogaster {{cite journal | author = Eagen KP, Hartl A, Kornberg RD| title = Stable chromosome condensation revealed by chromosome conformation capture | journal = Cell | volume = 163 | pages = 934–946 | year = 2015 | issue = 4 | doi = 10.1016/j.cell.2015.10.026 | pmid = 26544940| pmc = 4639323 }}
• Cell cycle dynamics and condensin-dependent chromatin reorganization in Schizosaccharomyces pombe {{cite journal | author = Kakui Y, Rabinowitz A, Barry DJ, Uhlmann F | title = Condensin-mediated remodeling of the mitotic chromatin landscape in fission yeast | journal = Nat Genet | doi = 10.1038/ng.3938 | year = 2017 | volume = 49 | issue = 10 | pages = 1553–1557 | pmid = 28825727| pmc = 5621628 }}
• Comparison of G1 and M phase chromosomes in Saccharomyces cerevisiae and the distinct effects of cohesin and condensin depletion {{cite journal | author = Schalbetter SA, Goloborodko A, Fudenberg G, Belton JM, Miles C, Yu M, Dekker J, Mirny L, Baxter J | title = SMC complexes differentially compact mitotic chromosomes according to genomic context | journal = Nat Cell Biol | volume = 19 | pages = 1071–1080 | year = 2017 | issue = 9 | doi = 10.1038/ncb3594 | pmid = 28825700| pmc = 5640152 }}
• Temporal changes in mitotic chromosomes in chicken DT40 cells {{cite journal | author = Gibcus JH, Samejima K, Goloborodko A, Samejima I, Naumova N, Nuebler J, Kanemaki MT, Xie L, Paulson JR, Earnshaw WC, Mirny LA, Dekker J | title = A pathway for mitotic chromosome formation | journal = Science | pages = eaao6135 | doi = 10.1126/science.aao6135 | year = 2018 | volume = 359 | issue = 6376 | pmid = 29348367| pmc = 5924687 }}
• Functional interplay between condensin and cohesin complexes in human cultured cells {{cite journal | author = Zhao H, Shu L, Qin S, Lyu F, Liu F, Lin E, Xia S, Wang B, Wang M, Shan F, Lin Y, Zhang L, Gu Y, Blobel GA, Huang K, Zhang H | title = Extensive mutual influences of SMC complexes shape 3D genome folding | journal = Nature | volume = 640 | issue = 8058 | pages = 543–553 | year = 2025 | doi = 10.1038/s41586-025-08638-3 | pmid = 40011778| bibcode = 2025Natur.640..543Z }} and chicken DT40 cells {{cite journal | author = Samejima K, Gibcus JH, Abraham S, Cisneros-Soberanis F, Samejima I, Beckett AJ, Puǎčeková N, Abad MA, Spanos C, Medina-Pritchard B, Paulson JR, Xie L, Jeyaprakash AA, Prior IA, Mirny LA, Dekker J, Goloborodko A, Earnshaw WC | title = Rules of engagement for condensins and cohesins guide mitotic chromosome formation | journal = Science | volume = 388 | issue = 6743 | pages = eadq1709 | year = 2025 | doi = 10.1126/science.adq1709 | pmid = 40208986| bibcode = 2025Sci...388q1709S }}
• Biochemical reconstitution
• Functional analysis of chromosomal proteins using Xenopus egg extracts{{cite journal | author = Kinoshita K, Kobayashi TJ, Hirano T| title = Balancing acts of two HEAT subunits of condensin I support dynamic assembly of chromosome axes | journal = Dev Cell | volume = 33 | issue = 1 | pages = 94–106 | year = 2015 | doi = 10.1016/j.devcel.2015.01.034 | pmid = 25850674}}{{cite journal | author = Kinoshita K, Tsubota Y, Tane S, Aizawa Y, Sakata R, Takeuchi K, Shintomi K, Nishiyama T, Hirano T | title = A loop extrusion-independent mechanism contributes to condensin I-mediated chromosome shaping | journal = J Cell Biol | volume = 221 | issue = 3 | pages = e202109016 | year = 2022 | doi = 10.1083/jcb.202109016 | pmid = 35045152| pmc = 8932526 }}{{cite journal|author=Shintomi K, Inoue F, Watanabe H, Ohsumi K, Ohsugi M, Hirano T|year=2017|title=Mitotic chromosome assembly despite nucleosome depletion in Xenopus egg extracts|journal=Science| volume=356 | issue = 6344 | pages = 1284–1287 |doi=10.1126/science.aam9702 | pmid =28522692|bibcode=2017Sci...356.1284S }}
• In vitro reconstitution of mitotic chromosomes using purified proteins
• Single-molecule techniques
• DNA compaction assays using magnetic tweezers{{cite journal | author = Strick TR, Kawaguchi T, Hirano T | title = Real-time detection of single-molecule DNA compaction by condensin I | journal = Curr Biol | volume = 14 | issue = 10 | pages = 874–880| year = 2004 | doi = 10.1016/j.cub.2004.04.038 | pmid = 15186743| bibcode = 2004CBio...14..874S }} and optical tweezers{{cite journal | author = Sun M, Amiri H, Tong AB, Shintomi K, Hirano T, Bustamante C, Heald R | title = Monitoring the compaction of single DNA molecules in Xenopus egg extract in real time | journal = Proc Natl Acad Sci USA | volume = 120 | issue = 12 | pages = e2221309120 | year = 2023 | doi = 10.1073/pnas.2221309120 | doi-access = free | pmid = 36917660| pmc = 10041109 | bibcode = 2023PNAS..12021309S }}
• Direct visualization of the motor activity of condensin{{cite journal | author = Terakawa T, Bisht S, Eeftens JM, Dekker C, Haering CH, Greene EC | title = The condensin complex is a mechanochemical motor that translocates along DNA | journal = Science| volume = 358 | issue = 6363 | pages = 672–676 | year = 2017 | doi = 10.1126/science.aan6516 | pmid =28882993| pmc = 5862036 | bibcode = 2017Sci...358..672T }}
• Direct visualization of loop extrusion by condensin{{cite journal | author = Ganji M, Shaltiel IA, Bisht S, Kim E, Kalichava A, Haering CH, Dekker C | title = Real-time imaging of DNA loop extrusion by condensin | journal = Science| volume = 360 | issue = 6384 | pages = 102–105 | year = 2018 | doi = 10.1126/science.aar7831 | pmid =29472443| pmc = 6329450 | bibcode = 2018Sci...360..102G }}
• Imaging-based approaches
• Cryo-electron tomography (Cryo-ET) for high-resolution 3D structure {{cite journal | author = Beel AJ, Azubel M, Mattei PJ, Kornberg RD | title = Structure of mitotic chromosomes | journal = Mol Cell | volume = 81 | pages = 4369–4376.e3 | year = 2021 | issue = 21 | doi = 10.1016/j.molcel.2021.08.020| pmid = 34520722 | pmc = 8571045 }}{{cite journal | author = McDonald A, Murre C, Sedat JW | title = Helical coiled nucleosome chromosome architectures during cell cycle progression | journal = Proc Natl Acad Sci U S A | volume = 121 | issue = 43 | pages = e2410584121 | year = 2024 | pmid = 39401359 | doi = 10.1073/pnas.2410584121| pmc = 11513933 | bibcode = 2024PNAS..12110584M }}
• Nano-scale 3D DNA tracing to map chromosome architecture {{cite journal | author = Beckwith KS, Brunner A, Morero NR, Jungmann R, Ellenberg J | title = Nanoscale DNA tracing reveals the self-organization mechanism of mitotic chromosomes | journal = Cell | volume = 186 | issue = 6 | pages = 1234–1245 | year = 2025 | pmid = 40132578 | doi = 10.1016/j.cell.2025.02.028| doi-access = free }}
• FAST CHIMP (Facilitated Segmentation and Tracking of Chromosomes in Mitosis Pipeline) for mitotic chromosome tracking {{cite journal | author = Stamatov R, Uzunova S, Kicheva Y, Karaboeva M, Blagoev T, Stoynov S | title = Supra-second tracking and live-cell karyotyping reveal principles of mitotic chromosome dynamics | journal = Nat Cell Biol | volume = 27 | issue = 4 | pages = 654–667 | year = 2025 | doi = 10.1038/s41556-025-01637-6 | pmid = 40185948| pmc = 11991918 }}
• Single-nucleosome imaging to analyze nucleosome dynamics within mitotic chromosomes {{cite journal | author = Hibino K, Sakai Y, Tamura S, Takagi M, Minami K, Natsume T, Shimazoe MA, Kanemaki MT, Imamoto N, Maeshima K | title = Single-nucleosome imaging unveils that condensins and nucleosome-nucleosome interactions differentially constrain chromatin to organize mitotic chromosomes | journal = Nat Commun | volume = 15 | issue = 1 | pages = 7152 | year = 2024 | doi = 10.1038/s41467-024-51454-y | pmid = 39169041 | pmc = 11339268 | bibcode = 2024NatCo..15.7152H }}
• Biophysical manipulation
• Micromanipulation with glass pipettes to measure mechanical properties of mitotic chromosomes {{cite journal | author = Poirier MG, Monhait T, Marko JF | title = Reversible hypercondensation and decondensation of mitotic chromosomes studied using combined chemical-micromechanical techniques | journal = J Cell Biochem | volume = 85 | issue = 2 | pages = 422–434 | year = 2002 | doi = 10.1002/jcb.10132 | pmid = 11948697}}{{cite journal | author = Poirier MG, Marko JF | title = Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold | journal = Proc Natl Acad Sci U S A | volume = 99 | issue = 24 | pages = 15393–15397 | year = 2002 | pmid = 12438695 | doi = 10.1073/pnas.232442599| doi-access = free | pmc = 137727 }}
• Optical tweezers-based micromanipulation to probe chromosomal elasticity and compaction {{cite journal | author = Meijering AEC, Sarlós K, Nielsen CF, Witt H, Harju J, Kerklingh E, Haasnoot GH, Bizard AH, Heller I, Broedersz CP, Liu Y, Peterman EJG, Hickson ID, Wuite GJL | title = Nonlinear mechanics of human mitotic chromosomes | journal = Nature | volume = 605 | issue = 7910 | pages = 545–550 | year = 2022 | pmid = 35508652 | doi = 10.1038/s41586-022-04666-5| pmc = 9117150 | bibcode = 2022Natur.605..545M }}{{cite journal | author = Witt H, Harju J, Chameau EMJ, Bruinsma CMA, Clement TVM, Nielsen CF, Hickson ID, Peterman EJG, Broedersz CP, Wuite GJL | title = Ion-mediated condensation controls the mechanics of mitotic chromosomes | journal = Nat Mater | volume = 23 | issue = 11 | pages = 1556–1562 | year = 2024 | pmid = 39284894 | doi = 10.1038/s41563-024-01975-0| pmc = 11525168 | bibcode = 2024NatMa..23.1556W }}
• Theoretical modeling and computational simulation
• Modeling mitotic chromosome assembly through a loop extrusion mechanism {{cite journal | author = Goloborodko A, Imakaev MV, Marko JF, Mirny L | title = Compaction and segregation of sister chromatids via active loop extrusion | journal = eLife | volume = 5 | page = doi: 10.7554/eLife.14864 | year = 2016 | doi = 10.7554/eLife.14864 | doi-access = free | pmid = 27192037| pmc = 4914367 }}
• Modeling mitotic chromosome assembly through a loop capture mechanism {{cite journal | author = Gerguri T, Fu X, Kakui Y, Khatri BS, Barrington C, Bates PA, Uhlmann F | title =Comparison of loop extrusion and diffusion capture as mitotic chromosome formation pathways in fission yeast | journal = Nucl Acids Res | volume = 49 | issue = 3 | pages = 1294–1312 | year = 2021 | doi =10.1093/nar/gkaa1270 | pmid = 33434270| pmc =7897502 }}
• Modeling mitotic chromosome assembly by incorporating condensin–condensin interactions {{cite journal | author = Sakai Y, Mochizuki A, Kinoshita K, Hirano T, Tachikawa M. | title = Modeling the functions of condensin in chromosome shaping and segregation | journal = PLOS Comput Biol | volume = 14 | issue = 6 | page = e1006152. doi: 10.1371/journal.pcbi.1006152 | year = 2018 | doi = 10.1371/journal.pcbi.1006152 | doi-access = free | pmid = 29912867| pmc = 6005465 | bibcode = 2018PLSCB..14E6152S }}
• Modeling mitotic chromosome assembly through a bridging-induced attraction mechanism {{cite journal | author = Forte G, Boteva L, Conforto F, Gilbert N, Cook PR, Marenduzzo D| title = Bridging condensins mediate compaction of mitotic chromosomes| journal = J Cell Biol | volume = 223 | issue = 1 | pages = e202209113 | year = 2024 | doi = 10.1083/jcb.202209113| pmid = 37976091| pmc = 10655892}}

File:BacCondensation4 E.png

Although bacteria lack histones, their genomic DNA associates with various nucleoid-associated proteins (NAPs) to form the nucleoid, a functional counterpart of the eukaryotic chromosome.

In bacteria, DNA compaction is facilitated by the introduction of negative supercoils (typically of the plectonemic type) by the enzyme DNA gyrase, a bacterial type II topoisomerase. In contrast, archaea possess histone-like proteins, and in some species, a nucleosome-like particle with ~60 base pair periodicity{{cite journal | author = Pereira SL, Grayling RA, Lurz R, Reeve JN | title = Archaeal nucleosomes | journal = Proc. Natl. Acad. Sci. USA| volume = 94 | pages = 12633–12637 | year = 2006 | issue = 23 | doi = 10.1073/pnas.94.23.12633 | doi-access = free | pmid =9356501| pmc = 25063 }} or an extended polymeric structure{{cite journal | author = Mattiroli F, Bhattacharyya S, Dyer PN, White AE, Sandman K, Burkhart BW, Byrne KR, Lee T, Ahn NG, Santangelo TJ, Reeve JN, Luger K | title = Structure of histone-based chromatin in Archaea | journal = Science | volume = 357 | issue = 6351 | pages = 609–612 | year = 2017 | pmid = 28798032 | doi = 10.1126/science.aaj1849| pmc = 5747315 }} have been observed. Recent advances in metagenomics and structure prediction algorithms have led to the discovery and classification of numerous histone-like proteins across prokaryotes.{{cite journal | author = Schwab S, Hu Y, van Erp B, Cajili MKM, Hartmann MD, Hernandez Alvarez B, Alva V, Boyle AL, Dame RT | title = Histones and histone variant families in prokaryotes | journal = Nat Commun | volume = 15 | issue = 1 | pages = 7950 | year = 2024 | pmid = 39261503 | doi = 10.1038/s41467-024-52337-y| pmc = 11390915 | bibcode = 2024NatCo..15.7950S }}

Many bacterial and archaeal species also possess SMC protein complexes analogous to eukaryotic condensins, including SMC–ScpAB and MukBEF, which play direct roles in organizing the nucleoid structure.{{cite journal | author = Graumann PL, Knust T | title = Dynamics of the bacterial SMC complex and SMC-like proteins involved in DNA repair | journal = Chromosome Res. | volume = 17 | pages = 265–275 | year = 2009 | issue = 2 | doi = 10.1007/s10577-008-9014-x | pmid = 19308706}}{{cite journal | author = Reyes-Lamothe R, Nicolas E, Sherratt DJ | title = Chromosome replication and segregation in bacteria | journal = Annu. Rev. Genet. | volume = 46 | pages = 121–143 | year = 2012 | doi = 10.1146/annurev-genet-110711-155421 | pmid = 22934648}}{{cite journal | author = Wang X, Montero Llopis P, Rudner DZ | title = Organization and segregation of bacterial chromosomes | journal = Nat. Rev. Genet. | volume = 14 | pages = 191–203 | year = 2013 | issue = 3 | doi = 10.1038/nrg3375 | pmid = 23400100| pmc = 3869393 }} Loss-of-function mutations in these complexes cause abnormal nucleoid morphology and defects in chromosome segregation. Thus, prokaryotes undergo a process functionally equivalent to chromosome condensation, which is critical for ensuring proper chromosome segregation within a spatially confined cell volume (Figure 4). Furthermore, Hi-C) technology has been applied to study the dynamics of nucleoid reorganization mediated by bacterial condensin in several model organisms, including Caulobacter crescentus,{{cite journal | author = Le TB, Imakaev MV, Mirny LA, Laub MT | title = High-resolution mapping of the spatial organization of a bacterial chromosome| journal = Science | volume = 342 | issue = 6159 | pages = 731–734 | year = 2013 | doi = 10.1126/science.1242059| pmid = 24158908| pmc = 3927313| bibcode = 2013Sci...342..731L}} Bacillus subtilis,{{cite journal | author = Wang X, Le TB, Lajoie BR, Dekker J, Laub MT, Rudner DZ | title = Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis| journal = Genes Dev. | volume = 29 | issue = 15 | pages = 1661–1675 | year = 2015 | doi = 10.1101/gad.265876.115| pmid = 26253537| pmc = 4536313}} and Escherichia coli.{{cite journal | author = Lioy VS, Cournac A, Marbouty M, Duigou S, Mozziconacci J, Espéli O, Boccard F, Koszul R | title = Multiscale Structuring of the E. coli Chromosome by Nucleoid-Associated and Condensin Proteins| journal = Cell | volume = 172 | issue = 4 | pages = 771–783.e18 | year = 2018 | doi = 10.1016/j.cell.2017.12.027| pmid = 29358050}}

The following table summarizes the similarities and differences in chromosome architecture between eukaryotes and prokaryotes. Such comparisons are crucial for redefining the process of chromosome condensation at the molecular level and for gaining insights into the evolutionary principles underlying higher-order chromosome organization.{{cite journal | author = Hirano T | title = Condensins and the evolution of torsion-mediated genome organization | journal = Trends Cell Biol.| volume = 24 | issue = 12 | pages = 727–733 | year = 2014 | doi = 10.1016/j.tcb.2014.06.007 | pmid = 25092191}}{{cite journal | author = Hirano T | title = Condensin-based chromosome organization from bacteria to vertebrates | journal = Cell | volume = 164 | issue = 5 | pages =847–857 | year = 2016| pmid =26919425}}

• chromosome / nucleoid
• mitosis / meiosis
• DNA / histone / nucleosome / chromatin
• condensin / cohesin / SMC protein / topoisomerase II
• DNA supercoil

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Category:Mitosis

Category:Meiosis

Category:Cell cycle