Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A

Takahashi, Motoko; Wakai, Toshifumi; Hirota, Toru

doi:10.1101/gad.282855.116

Cited by 36 publications

(58 citation statements)

References 24 publications

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“…Our simulations also show that to achieve agreement with Hi-C data, chromatin should also be condensed (computationally analogous to poor solvent conditions) forming densely packed chromatin loops within mitotic chromosomes analogous to the dense packing of chromatin observed in mitotic chromosomes by electron microscopy (41,74,75). The molecular basis for this condensation is not known but may involve mitosis-specific chromatin modifications (76,77) or active motor proteins such as KIF4A (78,79).…”

Section: Possible Mechanismssupporting

confidence: 60%

Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays

Samejima

Goloborodko

et al. 2017

Preprint

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During mitosis, chromosomes fold into compacted rod shaped structures. We combined imaging and Hi-C of synchronous DT40 cell cultures with polymer simulations to determine how interphase chromosomes are converted into compressed arrays of loops characteristic of mitotic chromosomes. We found that the interphase organization is disassembled within minutes of prophase entry and by late prophase chromosomes are already folded as arrays of consecutive loops. During prometaphase, this array reorganizes to form a helical arrangement of nested loops. Polymer simulations reveal that Hi-C data are inconsistent with solenoidal coiling of the entire chromatid, but instead suggest a centrally located helically twisted axis from which consecutive loops emanate as in a spiral staircase. Chromosomes subsequently shorten through progressive helical winding, with the numbers of loops per turn increasing so that the size of a helical turn grows from around 3 Mb (~40 loops) to ~12 Mb (~150 loops) in fully condensed metaphase chromosomes. Condensin is essential to disassemble the interphase chromatin conformation. Analysis of mutants revealed differing roles for condensin I and II during these processes. Either condensin can mediate formation of loop arrays. However, condensin II was required for helical winding during prometaphase, whereas condensin I modulated the size and arrangement of loops inside the helical turns. These observations identify a mitotic chromosome morphogenesis pathway in which folding of linear loop arrays produces long thin chromosomes during prophase that then shorten by progressive growth of loops and helical winding during prometaphase. One Sentence Summary:Mitotic chromosome morphogenesis occurs through condensin-mediated disassembly of the interphase conformation and formation of extended prophase loop arrays that then shorten by loop growth and condensin-dependent helical winding.

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Section: Possible Mechanismssupporting

confidence: 60%

Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays

Samejima

Goloborodko

et al. 2017

Preprint

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“…Our simulations also show that to achieve agreement with Hi-C data, chromatin should also be condensed (computationally analogous to poor solvent conditions) forming densely packed chromatin loops within mitotic chromosomes analogous to the dense packing of chromatin observed in mitotic chromosomes by electron microscopy (46, 78, 79). The molecular basis for this condensation is not known but may involve mitosis-specific chromatin modifications (80, 81) or active motor proteins such as KIF4A (82, 83). …”

Section: Discussionmentioning

confidence: 99%

A pathway for mitotic chromosome formation

Gibcus

Samejima

Goloborodko

et al. 2018

Science

653

106

871

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Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C of synchronous DT40 cell cultures with polymer simulations. We show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner and arrays of consecutive 60 kb loops are formed. During prometaphase ~80 kb inner loops are nested within ~400 kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral-staircase condensin scaffold. The size of helical turns progressively increases during prometaphase to ~12 Mb. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins while condensin II is required for helical winding.

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“…The condensin I complex plays an important role in chromosome condensation and segregation. 12,13 The aberrant expression of the subunits of the complex causes incomplete chromosome condensation. 14 NCAPH is a part of the condensin complex.…”

Section: Discussionmentioning

confidence: 99%

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

Sun

Huang

Wang

et al. 2019

Molecular Carcinogenesis

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Non‐SMC condensing I complex subunit H (NCAPH) is a member of the Barr protein family and part of the condensin I complex. The upregulation of NCAPH is associated with poor prognosis in patients with colon cancer. However, the relationship between NCAPH and hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore NCAPH expression in HCC tissues and to investigate NCAPH functions in HCC cells. In this study, we found that high expression of NCAPH in HCC indicated worse prognosis via bioinformatics analysis. Consistently, quantitative real‐time polymerase chain reaction assays in 20 pairs of HCC specimens and the immunohistochemical analysis of 100 HCC tissues showed the upregulation of NCAPH. We established stable NCAPH‐overexpressing and NCAPH knockdown cell lines. Cell Counting Kit‐8 assays and colony formation assay were performed to analyze cell proliferation. Migration and invasion were analyzed by Transwell assays. Subcutaneous xenograft models were used to explore the role of NCAPH in tumor formation in vivo. Our results showed that NCAPH promoted tumor proliferation, migration, and invasion in vitro and in vivo. In conclusion, our findings indicate that NCAPH could serve as a novel prognostic biomarker and a potential therapeutic target for patients with HCC.

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Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A

Cited by 36 publications

References 24 publications

Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays

Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays

A pathway for mitotic chromosome formation

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

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