Mitotic Chromosome Condensation Resets Chromatin to Safeguard Transcriptional Homeostasis During Interphase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2023 Jan 19

PMID 36656860

Authors

Lucia Ramos-Alonso

Petter Holland

Stephanie Le Gras

Xu Zhao

Bernard Jost

Magnar Bjoras

Yves Barral

Jorrit M Enserink

Pierre Chymkowitch

Affiliations

Soon will be listed here.

Abstract

Mitotic entry correlates with the condensation of the chromosomes, changes in histone modifications, exclusion of transcription factors from DNA, and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting of transcription. Rather, in the following interphase, the affected chromosome contains unusually high levels of the transcription machinery, resulting in abnormally high expression levels of genes , including various transcription factors. This subsequently causes the activation of inducible transcriptional programs , such as the genes, even in the absence of the relevant stimuli. Thus, mitotic chromosome condensation exerts stringent control on interphase gene expression to ensure the maintenance of basic cellular functions and cell identity across cell divisions. Together, our study identifies the maintenance of transcriptional homeostasis during interphase as an unexpected function of mitosis and mitotic chromosome condensation.

Citing Articles

Screening of obstructive sleep apnea and diabetes mellitus -related biomarkers based on integrated bioinformatics analysis and machine learning.

Yang J, Han Y, Diao X, Yuan B, Gu J Sleep Breath. 2025; 29(1):74.

PMID: 39804507 PMC: 11729194. DOI: 10.1007/s11325-024-03240-9.

Single-nucleus atlas of the Artemia female reproductive system suggests germline repression of the Z chromosome.

Elkrewi M, Vicoso B PLoS Genet. 2024; 20(8):e1011376.

PMID: 39213449 PMC: 11392275. DOI: 10.1371/journal.pgen.1011376.

Transcriptional repression across mitosis: mechanisms and functions.

Contreras A, Perea-Resa C Biochem Soc Trans. 2024; 52(1):455-464.

PMID: 38372373 PMC: 10903446. DOI: 10.1042/BST20231071.

Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole.

Corrales J, Ramos-Alonso L, Gonzalez-Sabin J, Rios-Lombardia N, Trevijano-Contador N, Engen Berg H Microbiol Spectr. 2024; 12(2):e0259423.

PMID: 38230926 PMC: 10845951. DOI: 10.1128/spectrum.02594-23.

Cyclin-dependent kinases: Masters of the eukaryotic universe.

Pluta A, Studniarek C, Murphy S, Norbury C Wiley Interdiscip Rev RNA. 2023; :e1816.

PMID: 37718413 PMC: 10909489. DOI: 10.1002/wrna.1816.

References

Granovskaia M, Jensen L, Ritchie M, Toedling J, Ning Y, Bork P . High-resolution transcription atlas of the mitotic cell cycle in budding yeast. Genome Biol. 2010; 11(3):R24. PMC: 2864564. DOI: 10.1186/gb-2010-11-3-r24. View

Kruitwagen T, Chymkowitch P, Denoth-Lippuner A, Enserink J, Barral Y . Centromeres License the Mitotic Condensation of Yeast Chromosome Arms. Cell. 2018; 175(3):780-795.e15. PMC: 6197839. DOI: 10.1016/j.cell.2018.09.012. View

Chymkowitch P, Eldholm V, Lorenz S, Zimmermann C, Lindvall J, Bjoras M . Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes. Proc Natl Acad Sci U S A. 2012; 109(26):10450-5. PMC: 3387082. DOI: 10.1073/pnas.1200067109. View

Neurohr G, Naegeli A, Titos I, Theler D, Greber B, Diez J . A midzone-based ruler adjusts chromosome compaction to anaphase spindle length. Science. 2011; 332(6028):465-8. DOI: 10.1126/science.1201578. View

Abramo K, Valton A, Venev S, Ozadam H, Fox A, Dekker J . A chromosome folding intermediate at the condensin-to-cohesin transition during telophase. Nat Cell Biol. 2019; 21(11):1393-1402. PMC: 6858582. DOI: 10.1038/s41556-019-0406-2. View

Palozola K, Donahue G, Liu H, Grant G, Becker J, Cote A . Mitotic transcription and waves of gene reactivation during mitotic exit. Science. 2017; 358(6359):119-122. PMC: 5727891. DOI: 10.1126/science.aal4671. View

Hsu J, Sun Z, Li X, Reuben M, Tatchell K, Bishop D . Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell. 2000; 102(3):279-91. DOI: 10.1016/s0092-8674(00)00034-9. View

Krishnan V, Nirantar S, Crasta K, Cheng A, Surana U . DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior. Mol Cell. 2004; 16(5):687-700. DOI: 10.1016/j.molcel.2004.11.001. View

Kruitwagen T, Denoth-Lippuner A, Wilkins B, Neumann H, Barral Y . Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation. Elife. 2015; 4:e1039. PMC: 4755758. DOI: 10.7554/eLife.10396. View

10.

Chang Y, Tseng S, Huang Y, Shen Z, Hsu P, Hsieh M . Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4. Nat Commun. 2017; 8(1):56. PMC: 5496861. DOI: 10.1038/s41467-017-00080-y. View

11.

Terhorst A, Sandikci A, Keller A, Whittaker C, Dunham M, Amon A . The environmental stress response causes ribosome loss in aneuploid yeast cells. Proc Natl Acad Sci U S A. 2020; 117(29):17031-17040. PMC: 7382292. DOI: 10.1073/pnas.2005648117. View

12.

Heyken W, Repenning A, Kumme J, Schuller H . Constitutive expression of yeast phospholipid biosynthetic genes by variants of Ino2 activator defective for interaction with Opi1 repressor. Mol Microbiol. 2005; 56(3):696-707. DOI: 10.1111/j.1365-2958.2004.04499.x. View

13.

Smurova K, De Wulf P . Centromere and Pericentromere Transcription: Roles and Regulation … in Sickness and in Health. Front Genet. 2019; 9:674. PMC: 6309819. DOI: 10.3389/fgene.2018.00674. View

14.

Zhang H, Emerson D, Gilgenast T, Titus K, Lan Y, Huang P . Chromatin structure dynamics during the mitosis-to-G1 phase transition. Nature. 2019; 576(7785):158-162. PMC: 6895436. DOI: 10.1038/s41586-019-1778-y. View

15.

Palozola K, Liu H, Nicetto D, Zaret K . Low-Level, Global Transcription during Mitosis and Dynamic Gene Reactivation during Mitotic Exit. Cold Spring Harb Symp Quant Biol. 2018; 82:197-205. DOI: 10.1101/sqb.2017.82.034280. View

16.

Raccaud M, Suter D . Transcription factor retention on mitotic chromosomes: regulatory mechanisms and impact on cell fate decisions. FEBS Lett. 2017; 592(6):878-887. DOI: 10.1002/1873-3468.12828. View

17.

Palozola K, Lerner J, Zaret K . A changing paradigm of transcriptional memory propagation through mitosis. Nat Rev Mol Cell Biol. 2018; 20(1):55-64. PMC: 6557398. DOI: 10.1038/s41580-018-0077-z. View

18.

Antonin W, Neumann H . Chromosome condensation and decondensation during mitosis. Curr Opin Cell Biol. 2016; 40:15-22. DOI: 10.1016/j.ceb.2016.01.013. View

19.

Liu Y, Pelham-Webb B, Di Giammartino D, Li J, Kim D, Kita K . Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells. Cell Rep. 2017; 19(7):1283-1293. PMC: 5495017. DOI: 10.1016/j.celrep.2017.04.067. View

20.

Warsi T, Navarro M, Bachant J . DNA topoisomerase II is a determinant of the tensile properties of yeast centromeric chromatin and the tension checkpoint. Mol Biol Cell. 2008; 19(10):4421-33. PMC: 2555933. DOI: 10.1091/mbc.e08-05-0547. View