Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription

Condensins are genome organisers that shape chromosomes and promote their accurate transmission. Several studies have also implicated condensins in gene expression, although the mechanisms have remained enigmatic. Here, we report on the role of condensin in gene expression in fission and budding yeasts. In contrast to previous studies, we provide compelling evidence that condensin plays no direct role in the maintenance of the transcriptome, neither during interphase nor during mitosis. We further show that the changes in gene expression in post-mitotic fission yeast cells that result from condensin inactivation are largely a consequence of chromosome missegregation during anaphase, which notably depletes the RNA-exosome from daughter cells. Crucially, preventing karyotype abnormalities in daughter cells restores a normal transcriptome despite condensin inactivation. Thus, chromosome instability, rather than a direct role of condensin in the transcription process, changes gene expression. This knowledge challenges the concept of gene regulation by canonical condensin complexes.

[1]  Histone H2A.Z , 2020, Definitions.

[2]  Sevinç Ercan,et al.  Condensin Depletion Causes Genome Decompaction Without Altering the Level of Global Gene Expression in Saccharomyces cerevisiae , 2018, Genetics.

[3]  Marjon S. van Ruiten,et al.  SMC Complexes: Universal DNA Looping Machines with Distinct Regulators. , 2018, Trends in genetics : TIG.

[4]  C. Dekker,et al.  Real-time imaging of DNA loop extrusion by condensin , 2018, Science.

[5]  J. Ellenberg,et al.  A quantitative map of human Condensins provides new insights into mitotic chromosome architecture , 2018, bioRxiv.

[6]  J. R. Paulson,et al.  A pathway for mitotic chromosome formation , 2018, Science.

[7]  Shveta Bisht,et al.  Structural Basis for a Safety-Belt Mechanism That Anchors Condensin to Chromosomes , 2017, Cell.

[8]  A. Raj,et al.  Mitotic transcription and waves of gene reactivation during mitotic exit , 2017, Science.

[9]  Erez Lieberman Aiden,et al.  Cohesin Loss Eliminates All Loop Domains , 2017, Cell.

[10]  Sevinç Ercan,et al.  Acute condensin depletion causes genome decompaction without altering the level of global gene expression in Saccharomyces cerevisiae , 2017, bioRxiv.

[11]  Jonathan Baxter,et al.  SMC complexes differentially compact mitotic chromosomes according to genomic context , 2017, Nature Cell Biology.

[12]  Brian D. Slaughter,et al.  Condensin II is anchored by TFIIIC and H3K4me3 in the mammalian genome and supports the expression of active dense gene clusters , 2017, Science Advances.

[13]  Rebecca R. Beach,et al.  Aneuploidy Causes Non-genetic Individuality , 2017, Cell.

[14]  Vincent Vanoosthuyse,et al.  The loading of condensin in the context of chromatin , 2016, Current Genetics.

[15]  Michael B. Mayhew,et al.  Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast , 2016, Current Biology.

[16]  Andreas Hochwagen,et al.  Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect within the Ribosomal DNA Array. , 2016, Cell reports.

[17]  D. Jamieson,et al.  Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability , 2016, Genes & development.

[18]  B. Paul,et al.  Altered RNA processing and export lead to retention of mRNAs near transcription sites and nuclear pore complexes or within the nucleolus , 2016, Molecular biology of the cell.

[19]  E. Nora,et al.  CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation. , 2016, Annual review of genomics and human genetics.

[20]  Osamu Iwasaki,et al.  Transcription factors mediate condensin recruitment and global chromosomal organization in fission yeast , 2016, Nature Genetics.

[21]  E. Chautard,et al.  Nucleosome eviction in mitosis assists condensin loading and chromosome condensation , 2016, The EMBO journal.

[22]  I. Hagan Chromatin and Cell Wall Staining of Schizosaccharomyces pombe. , 2016, Cold Spring Harbor protocols.

[23]  M. Gullerová,et al.  Transcription facilitates sister chromatid cohesion on chromosomal arms , 2016, Nucleic acids research.

[24]  F. Uhlmann SMC complexes: from DNA to chromosomes , 2016, Nature Reviews Molecular Cell Biology.

[25]  Lior Pachter,et al.  Near-optimal probabilistic RNA-seq quantification , 2016, Nature Biotechnology.

[26]  T. Hirano,et al.  Condensin-Based Chromosome Organization from Bacteria to Vertebrates , 2016, Cell.

[27]  Andreas Hochwagen,et al.  Condensin Promotes Position Effects within Tandem DNA Repeats via the RITS Complex. , 2016, Cell reports.

[28]  Andreas Hochwagen,et al.  Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect within the Ribosomal DNA Array. , 2016, Cell reports.

[29]  L. Vasiljeva,et al.  The regulation and functions of the nuclear RNA exosome complex , 2016, Nature Reviews Molecular Cell Biology.

[30]  J. Wilusz Removing roadblocks to deep sequencing of modified RNAs , 2015, Nature Methods.

[31]  A. Amon,et al.  Short- and long-term effects of chromosome mis-segregation and aneuploidy , 2015, Nature Reviews Molecular Cell Biology.

[32]  Xiaoping Zhou,et al.  Condensin I and II Complexes License Full Estrogen Receptor α-Dependent Enhancer Activation. , 2015, Molecular cell.

[33]  T. Sugiyama,et al.  The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the nuclear exosome , 2015, Nature Communications.

[34]  Laurent Modolo,et al.  UrQt: an efficient software for the Unsupervised Quality trimming of NGS data , 2015, BMC Bioinformatics.

[35]  M. Yanagida,et al.  RNA pol II transcript abundance controls condensin accumulation at mitotically up-regulated and heat-shock-inducible genes in fission yeast , 2015, Genes to cells : devoted to molecular & cellular mechanisms.

[36]  Andre J. Faure,et al.  Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin , 2015, Genome research.

[37]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[38]  Mark Gerstein,et al.  MUSIC: identification of enriched regions in ChIP-Seq experiments using a mappability-corrected multiscale signal processing framework , 2014, Genome Biology.

[39]  J. Bähler,et al.  The RNA exosome promotes transcription termination of backtracked RNA polymerase II , 2014, Nature Structural &Molecular Biology.

[40]  Masayuki Yamamoto,et al.  Optimization of the analogue-sensitive Cdc2/Cdk1 mutant by in vivo selection eliminates physiological limitations to its use in cell cycle analysis , 2014, Open Biology.

[41]  T. Le Bihan,et al.  CPF-Associated Phosphatase Activity Opposes Condensin-Mediated Chromosome Condensation , 2014, PLoS genetics.

[42]  Jill M Dowen,et al.  SMC complexes link gene expression and genome architecture. , 2014, Current opinion in genetics & development.

[43]  K. Shirahige,et al.  Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells , 2014, Cell cycle.

[44]  J. Desvignes,et al.  A Genetic Screen for Functional Partners of Condensin in Fission Yeast , 2013, G3: Genes, Genomes, Genetics.

[45]  C. Haering,et al.  Entrapment of chromosomes by condensin rings prevents their breakage during cytokinesis. , 2013, Developmental cell.

[46]  B. Abraham,et al.  Multiple Structural Maintenance of Chromosome Complexes at Transcriptional Regulatory Elements , 2013, Stem cell reports.

[47]  Sevinç Ercan,et al.  Genome-wide analysis of condensin binding in Caenorhabditis elegans , 2013, Genome Biology.

[48]  A. Oshlack,et al.  Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes , 2013, Nature Communications.

[49]  C. Glass,et al.  Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation , 2013, Nature.

[50]  Barbara J Meyer,et al.  Condensin controls recruitment of RNA polymerase II to achieve nematode X-chromosome dosage compensation , 2013, eLife.

[51]  Christophe Zimmer,et al.  FISH-quant: automatic counting of transcripts in 3D FISH images , 2013, Nature Methods.

[52]  H. Yokota,et al.  Local nucleosome dynamics facilitate chromatin accessibility in living mammalian cells. , 2012, Cell reports.

[53]  K. Miura,et al.  Quantitative Analysis of Chromosome Condensation in Fission Yeast , 2012, Molecular and Cellular Biology.

[54]  Maitreya J. Dunham,et al.  Transcriptional consequences of aneuploidy , 2012, Proceedings of the National Academy of Sciences.

[55]  A. Amon,et al.  Chromosomal instability and aneuploidy in cancer: from yeast to man , 2012, EMBO reports.

[56]  S. Ramaswamy,et al.  A Shared Role for RBF1 and dCAP-D3 in the Regulation of Transcription with Consequences for Innate Immunity , 2012, PLoS genetics.

[57]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[58]  J. Rosenfeld,et al.  Condensin dysfunction in human cells induces nonrandom chromosomal breaks in anaphase, with distinct patterns for both unique and repeated genomic regions , 2011, Chromosoma.

[59]  C. Haering,et al.  Condensin structures chromosomal DNA through topological links , 2011, Nature Structural &Molecular Biology.

[60]  M. Yanagida,et al.  Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2 , 2011, Journal of Cell Science.

[61]  Marcel Martin Cutadapt removes adapter sequences from high-throughput sequencing reads , 2011 .

[62]  J. Javerzat,et al.  Psm3 Acetylation on Conserved Lysine Residues Is Dispensable for Viability in Fission Yeast but Contributes to Eso1-Mediated Sister Chromatid Cohesion by Antagonizing Wpl1 , 2011, Molecular and Cellular Biology.

[63]  J. Ihle,et al.  Chromatin condensation via the condensin II complex is required for peripheral T‐cell quiescence , 2011, The EMBO journal.

[64]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[65]  Masayuki Yamamoto,et al.  Importance of polyadenylation in the selective elimination of meiotic mRNAs in growing S. pombe cells , 2010, The EMBO journal.

[66]  S. Grewal,et al.  Centromeric Localization of Dispersed Pol III Genes in Fission Yeast , 2010, Molecular biology of the cell.

[67]  A. Emili,et al.  An acetylated form of histone H2A.Z regulates chromosome architecture in Schizosaccharomyces pombe , 2009, Nature Structural &Molecular Biology.

[68]  Ming Zhou,et al.  Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs , 2009, Nature.

[69]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[70]  C. K. Schmidt,et al.  Conserved features of cohesin binding along fission yeast chromosomes , 2009, Genome Biology.

[71]  E. Andrulis,et al.  Core exosome-independent roles for Rrp6 in cell cycle progression. , 2009, Molecular biology of the cell.

[72]  L. Steinmetz,et al.  Bidirectional promoters generate pervasive transcription in yeast , 2009, Nature.

[73]  P. Warburton,et al.  Analysis of the largest tandemly repeated DNA families in the human genome , 2008, BMC Genomics.

[74]  T. Itoh,et al.  Identification of cis-acting sites for condensin loading onto budding yeast chromosomes. , 2008, Genes & development.

[75]  K. Shirahige,et al.  Condensin-Dependent rDNA Decatenation Introduces a Temporal Pattern to Chromosome Segregation , 2008, Current Biology.

[76]  I. Goodhead,et al.  Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution , 2008, Nature.

[77]  M. Yanagida,et al.  Dissection of the essential steps for condensin accumulation at kinetochores and rDNAs during fission yeast mitosis , 2008, The Journal of cell biology.

[78]  N. Proudfoot,et al.  Cohesin Complex Promotes Transcriptional Termination between Convergent Genes in S. pombe , 2008, Cell.

[79]  Steven P. Gygi,et al.  RNAi-Dependent and -Independent RNA Turnover Mechanisms Contribute to Heterochromatic Gene Silencing , 2007, Cell.

[80]  Y. Hiraoka,et al.  Selective elimination of messenger RNA prevents an incidence of untimely meiosis , 2006, Nature.

[81]  T. Toda,et al.  Inactivation of the Pre-mRNA Cleavage and Polyadenylation Factor Pfs2 in Fission Yeast Causes Lethal Cell Cycle Defects , 2005, Molecular and Cellular Biology.

[82]  T. Misteli,et al.  Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins , 2005, The Journal of cell biology.

[83]  M. Yanagida,et al.  The nucleolus is involved in mRNA export from the nucleus in fission yeast , 2004, Journal of Cell Science.

[84]  F. Uhlmann,et al.  Cdc14 Phosphatase Induces rDNA Condensation and Resolves Cohesin-Independent Cohesion during Budding Yeast Anaphase , 2004, Cell.

[85]  J. Lis,et al.  The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila , 2002, Nature.

[86]  A. Murray,et al.  Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior. , 2002, Molecular biology of the cell.

[87]  Matthias Sipiczki,et al.  Where does fission yeast sit on the tree of life? , 2000, Genome Biology.

[88]  A. Strunnikov,et al.  The Condensin Complex Governs Chromosome Condensation and Mitotic Transmission of Rdna , 2000, The Journal of cell biology.

[89]  M. Yanagida,et al.  Fission yeast condensin complex: essential roles of non-SMC subunits for condensation and Cdc2 phosphorylation of Cut3/SMC4. , 1999, Genes & development.

[90]  K. Gould,et al.  Isolation and characterization of new fission yeast cytokinesis mutants. , 1998, Genetics.

[91]  M. Yanagida,et al.  Mis6, a Fission Yeast Inner Centromere Protein, Acts during G1/S and Forms Specialized Chromatin Required for Equal Segregation , 1997, Cell.

[92]  P. Nurse,et al.  cdc12p, a Protein Required for Cytokinesis in Fission Yeast, Is a Component of the Cell Division Ring and Interacts with Profilin , 1997, The Journal of cell biology.

[93]  M. Yanagida,et al.  Fission yeast cut3 and cut14, members of a ubiquitous protein family, are required for chromosome condensation and segregation in mitosis. , 1994, The EMBO journal.

[94]  M. Nichols,et al.  Interaction of yeast transcription factor IIIC with dimeric Schizosaccharomyces pombe tRNA(Ser)-tRNA(Met) genes. , 1989, The Journal of biological chemistry.

[95]  O. Niwa,et al.  Triploid meiosis and aneuploidy in Schizosaccharomyces pombe: an unstable aneuploid disomic for chromosome III , 1985, Current Genetics.

[96]  T. Toda,et al.  The NDA3 gene of fission yeast encodes β-tubulin: A cold-sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis , 1984, Cell.

[97]  V. Orlando,et al.  Drosophila chromosome condensation proteins Topoisomerase II and Barren colocalize with Polycomb and maintain Fab-7 PRE silencing. , 2001, Molecular cell.

[98]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.

[99]  B. Seshachar,et al.  The nucleolus. , 1946, Current science.

[100]  J. R.,et al.  Quantitative analysis , 1892, Nature.