A mitotic chromatin phase transition prevents perforation by microtubules

Maximilian W.G. Schneider; Bryan A. Gibson; Shotaro Otsuka; Maximilian F.D. Spicer; Mina Petrovic; Claudia Blaukopf; Christoph C.H. Langer; Paul Batty; Thejaswi Nagaraju; Lynda K. Doolittle; Michael K. Rosen; Daniel W. Gerlich

doi:10.1038/s41586-022-05027-y

A mitotic chromatin phase transition prevents perforation by microtubules

Maximilian W.G. Schneider
, Bryan A. Gibson
, Shotaro Otsuka
, Maximilian F.D. Spicer
, Mina Petrovic
, Claudia Blaukopf
, Christoph C.H. Langer
, Paul Batty
, Thejaswi Nagaraju
, Lynda K. Doolittle
, Michael K. Rosen
, Daniel W. Gerlich

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells^1–3. Assembly of mitotic chromosomes involves DNA looping by condensin^4–8 and chromatin compaction by global histone deacetylation^9–13. Although condensin confers mechanical resistance to spindle pulling forces^14–16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.

Original language	English
Pages (from-to)	183-190
Number of pages	8
Journal	Nature
Volume	609
Issue number	7925
DOIs	https://doi.org/10.1038/s41586-022-05027-y
Publication status	Published - 1 Sept 2022

Funding

We thank the staff at the IMBA/IMP/GMI BioOptics and Molecular Biology Service and the VBCF Electron Microscopy and Protein Technologies facilities for technical support; I. Patten, A. Khodjakov, H. Maiato and C. Janke for comments on the manuscript; A. M. Rodrigues Viana for advice and reagents for genome engineering. Research in the laboratory of D.W.G. is supported by the Austrian Academy of Sciences, the Austrian Science Fund (FWF; Doktoratskolleg ‘Chromosome Dynamics’ DK W1238), the Vienna Science and Technology Fund (WWTF; projects LS17-003 and LS19-001), and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101019039). Research in the laboratory of S.O. is supported by the Vienna Science and Technology Fund (WWTF; project LS19-001). Research in the laboratory of M.K.R. is supported by the Howard Hughes Medical Institute, a Paul G. Allen Frontiers Distinguished Investigator Award (to M.K.R.) and grants from the NIH (F32GM129925 to B.A.G.) and the Welch Foundation (I-1544 to M.K.R.). M.W.G.S. and M.P. have received a PhD fellowship from the Boehringer Ingelheim Fonds. T.N. has received a fellowship from the VIP2 postdoc program.

Austrian Fields of Science 2012

106023 Molecular biology

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@article{044a5f2256b54a0697709315401809a1,

title = "A mitotic chromatin phase transition prevents perforation by microtubules",

abstract = "Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1–3. Assembly of mitotic chromosomes involves DNA looping by condensin4–8 and chromatin compaction by global histone deacetylation9–13. Although condensin confers mechanical resistance to spindle pulling forces14–16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.",

author = "Schneider, \{Maximilian W.G.\} and Gibson, \{Bryan A.\} and Shotaro Otsuka and Spicer, \{Maximilian F.D.\} and Mina Petrovic and Claudia Blaukopf and Langer, \{Christoph C.H.\} and Paul Batty and Thejaswi Nagaraju and Doolittle, \{Lynda K.\} and Rosen, \{Michael K.\} and Gerlich, \{Daniel W.\}",

note = "Funding Information: We thank the staff at the IMBA/IMP/GMI BioOptics and Molecular Biology Service and the VBCF Electron Microscopy and Protein Technologies facilities for technical support; I. Patten, A. Khodjakov, H. Maiato and C. Janke for comments on the manuscript; A. M. Rodrigues Viana for advice and reagents for genome engineering. Research in the laboratory of D.W.G. is supported by the Austrian Academy of Sciences, the Austrian Science Fund (FWF; Doktoratskolleg {\textquoteleft}Chromosome Dynamics{\textquoteright} DK W1238), the Vienna Science and Technology Fund (WWTF; projects LS17-003 and LS19-001), and the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement no. 101019039). Research in the laboratory of S.O. is supported by the Vienna Science and Technology Fund (WWTF; project LS19-001). Research in the laboratory of M.K.R. is supported by the Howard Hughes Medical Institute, a Paul G. Allen Frontiers Distinguished Investigator Award (to M.K.R.) and grants from the NIH (F32GM129925 to B.A.G.) and the Welch Foundation (I-1544 to M.K.R.). M.W.G.S. and M.P. have received a PhD fellowship from the Boehringer Ingelheim Fonds. T.N. has received a fellowship from the VIP2 postdoc program. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = sep,

day = "1",

doi = "10.1038/s41586-022-05027-y",

language = "English",

volume = "609",

pages = "183--190",

journal = "Nature",

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number = "7925",

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T1 - A mitotic chromatin phase transition prevents perforation by microtubules

AU - Schneider, Maximilian W.G.

AU - Gibson, Bryan A.

AU - Otsuka, Shotaro

AU - Spicer, Maximilian F.D.

AU - Petrovic, Mina

AU - Blaukopf, Claudia

AU - Langer, Christoph C.H.

AU - Batty, Paul

AU - Nagaraju, Thejaswi

AU - Doolittle, Lynda K.

AU - Rosen, Michael K.

AU - Gerlich, Daniel W.

N1 - Funding Information: We thank the staff at the IMBA/IMP/GMI BioOptics and Molecular Biology Service and the VBCF Electron Microscopy and Protein Technologies facilities for technical support; I. Patten, A. Khodjakov, H. Maiato and C. Janke for comments on the manuscript; A. M. Rodrigues Viana for advice and reagents for genome engineering. Research in the laboratory of D.W.G. is supported by the Austrian Academy of Sciences, the Austrian Science Fund (FWF; Doktoratskolleg ‘Chromosome Dynamics’ DK W1238), the Vienna Science and Technology Fund (WWTF; projects LS17-003 and LS19-001), and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101019039). Research in the laboratory of S.O. is supported by the Vienna Science and Technology Fund (WWTF; project LS19-001). Research in the laboratory of M.K.R. is supported by the Howard Hughes Medical Institute, a Paul G. Allen Frontiers Distinguished Investigator Award (to M.K.R.) and grants from the NIH (F32GM129925 to B.A.G.) and the Welch Foundation (I-1544 to M.K.R.). M.W.G.S. and M.P. have received a PhD fellowship from the Boehringer Ingelheim Fonds. T.N. has received a fellowship from the VIP2 postdoc program. Publisher Copyright: © 2022, The Author(s).

PY - 2022/9/1

Y1 - 2022/9/1

N2 - Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1–3. Assembly of mitotic chromosomes involves DNA looping by condensin4–8 and chromatin compaction by global histone deacetylation9–13. Although condensin confers mechanical resistance to spindle pulling forces14–16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.

AB - Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1–3. Assembly of mitotic chromosomes involves DNA looping by condensin4–8 and chromatin compaction by global histone deacetylation9–13. Although condensin confers mechanical resistance to spindle pulling forces14–16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.

UR - https://www.scopus.com/pages/publications/85135333718

U2 - 10.1038/s41586-022-05027-y

DO - 10.1038/s41586-022-05027-y

M3 - Article

C2 - 35922507

AN - SCOPUS:85135333718

SN - 0028-0836

VL - 609

SP - 183

EP - 190

JO - Nature

JF - Nature

IS - 7925

ER -

A mitotic chromatin phase transition prevents perforation by microtubules

Abstract

Funding

Austrian Fields of Science 2012

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