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

2018 ◽  
Author(s):  
Clémence Hocquet ◽  
Xavier Robellet ◽  
Laurent Modolo ◽  
Xi-Ming Sun ◽  
Claire Burny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromosome Instability ◽  
Yeast Cells ◽  
Compelling Evidence ◽  
Direct Role ◽  
Daughter Cells ◽  
Transcription Process ◽  
Rna Exosome ◽  
Segregation Of Chromosomes

AbstractCondensins 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.

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

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Clémence Hocquet ◽  
Xavier Robellet ◽  
Laurent Modolo ◽  
Xi-Ming Sun ◽  
Claire Burny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromosome Instability ◽  
Yeast Cells ◽  
Compelling Evidence ◽  
Direct Role ◽  
Daughter Cells ◽  
Transcription Process ◽  
Rna Exosome ◽  
Segregation Of Chromosomes

Condensins are genome organisers that shape chromosomes and promote their accurate transmission. Several studies have also implicated condensins in gene expression, although any 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.

The Role of Nuclear Stiffness and Resilience in Mechanotransduction

2010 ◽  
Author(s):  
Kris Noel Dahl ◽  
Elizabeth A. Booth-Gauthier ◽  
Alexandre J. S. Ribeiro ◽  
Zhixia Zhong
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Live Cell Imaging ◽  
Volume Fraction ◽  
Direct Role ◽  
Intact Cells ◽  
Large Volume Fraction ◽  
Nuclear Mechanics ◽  
Model Cell

Mechanical force is found to be increasingly important during development and for proper homeostatic maintenance of cells and tissues. The nucleus occupies a large volume fraction of the cell and is interconnected with the cytoskeleton. Here, to determine the direct role of the nucleus itself in converting forces to changes in gene expression, also known as, mechanotransduction, we examine changes in nuclear mechanics and gene reorganization associated with cell fate and with extracellular force. We measure mechanics of nuclei in many model cell systems using micropipette aspiration to show changes in nuclear mechanics. In intact cells we characterize the rheological changes induced in the genome organization with live cell imaging and particle tracking, and we suggest how these changes relate to gene expression.

scholarly journals Polyamine-modulated factor 1 binds to the human homologue of the 7a subunit of the Arabidopsis COP9 signalosome: implications in gene expression

2002 ◽  
Vol 366 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Yanlin WANG ◽  
Wendy DEVEREUX ◽  
Tracy M. STEWART ◽  
Robert A. CASERO
Keyword(s):  
Gene Expression ◽  
Coiled Coil ◽  
Cop9 Signalosome ◽  
Related Factor ◽  
Human Homologue ◽  
Direct Role ◽  
Hybrid Strategy ◽  
Protein Partners ◽  
Responsive Element

Polyamines have been identified to play a role in the transcription of various growth-related genes. The recently discovered polyamine responsive element and the associated trans-acting proteins involved in polyamine-regulated transcription have provided a model system for the study of the role of polyamines in transcription. Polyamine-modulated factor 1 (PMF-1) was identified as one of the transacting factors that binds to NF-E2 related factor-2 (Nrf-2) to regulate the transcription of spermidine/spermine N1-acetyltransferase (SSAT). The possibility that PMF-1 also binds to other proteins involved in transcriptional regulation cannot be ruled out. Using a yeast two-hybrid strategy, it was found that PMF-1 binds to a human homologue of the Arabidopsis COP9 signalosome subunit 7a (CSN 7) protein. In the present study, we describe human CSN 7, a 275-amino-acid- containing protein that may have a direct role in regulating gene expression. CSN 7 and PMF-1 bind to each other, as well as compete with each other for binding to Nrf-2. This competition for Nrf-2 binding and interaction with each other is implicated in the regulation of SSAT transcription. CSN 7 possesses a C-terminal coiled-coil domain similar to the domain that mediates the interaction between PMF-1 and Nrf-2, suggesting that coiled-coil domains also mediate the interaction between CSN 7 and PMF-1. Since CSN 7 does not contain a DNA-binding domain, its effects on transcription must occur in conjunction with binding to other proteins. The results presented here demonstrate that PMF-1 and Nrf-2 can act as protein partners of CSN 7.

scholarly journals The Role of Human Centromeric RNA in Chromosome Stability

2021 ◽  
Vol 8 ◽  
Author(s):  
Simon Leclerc ◽  
Katsumi Kitagawa
Keyword(s):  
Satellite Dna ◽  
Cellular Structure ◽  
Chromosome Instability ◽  
Short Review ◽  
Chromosome Stability ◽  
Alpha Satellite ◽  
Alpha Satellite Dna ◽  
Segregation Of Chromosomes

Chromosome instability is a hallmark of cancer and is caused by inaccurate segregation of chromosomes. One cellular structure used to avoid this fate is the kinetochore, which binds to the centromere on the chromosome. Human centromeres are poorly understood, since sequencing and analyzing repeated alpha-satellite DNA regions, which can span a few megabases at the centromere, are particularly difficult. However, recent analyses revealed that these regions are actively transcribed and that transcription levels are tightly regulated, unveiling a possible role of RNA at the centromere. In this short review, we focus on the recent discovery of the function of human centromeric RNA in the regulation and structure of the centromere, and discuss the consequences of dysregulation of centromeric RNA in cancer.

scholarly journals Kinesin-like Protein CHO1 Is Required for the Formation of Midbody Matrix and the Completion of Cytokinesis in Mammalian Cells

2002 ◽  
Vol 13 (6) ◽  
pp. 1832-1845 ◽  
Author(s):  
Jurgita Matuliene ◽  
Ryoko Kuriyama
Keyword(s):  
Binding Site ◽  
Mammalian Cells ◽  
Cytoplasmic Bridge ◽  
Central Spindle ◽  
Atp Binding Site ◽  
Daughter Cells ◽  
Dividing Cells ◽  
Spindle Midzone ◽  
Segregation Of Chromosomes

CHO1 is a mammalian kinesin-like motor protein of the MKLP1 subfamily. It associates with the spindle midzone during anaphase and concentrates to a midbody matrix during cytokinesis. CHO1 was originally implicated in karyokinesis, but the invertebrate homologues of CHO1 were shown to function in the midzone formation and cytokinesis. To analyze the role of the protein in mammalian cells, we mutated the ATP-binding site of CHO1 and expressed it in CHO cells. Mutant protein (CHO1F′) was able to interact with microtubules via ATP-independent microtubule-binding site(s) but failed to accumulate at the midline of the central spindle and affected the localization of endogenous CHO1. Although the segregation of chromosomes, the bundling of midzone microtubules, and the initiation of cytokinesis proceeded normally in CHO1F′-expressing cells, the completion of cytokinesis was inhibited. Daughter cells were frequently entering interphase while connected by a microtubule-containing cytoplasmic bridge from which the dense midbody matrix was missing. Depletion of endogenous CHO1 via RNA-mediated interference also affected the formation of midbody matrix in dividing cells, caused the disorganization of midzone microtubules, and resulted in abortive cytokinesis. Thus, CHO1 may not be required for karyokinesis, but it is essential for the proper midzone/midbody formation and cytokinesis in mammalian cells.

scholarly journals RIP140-Targeted Repression of Gene Expression in Adipocytes

2005 ◽  
Vol 25 (21) ◽  
pp. 9383-9391 ◽  
Author(s):  
Mark Christian ◽  
Evangelos Kiskinis ◽  
Darja Debevec ◽  
Göran Leonardsson ◽  
Roger White ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Expenditure ◽  
Uncoupling Protein ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Direct Role ◽  
Enhancer Element ◽  
Adipose Cells

ABSTRACT Ligand-dependent repression of nuclear receptor activity forms a novel mechanism for regulating gene expression. To investigate the intrinsic role of the corepressor RIP140, we have monitored gene expression profiles in cells that express or lack the RIP140 gene and that can be induced to undergo adipogenesis in vitro. In contrast to normal white adipose tissue and in vitro-differentiated wild-type adipocytes, RIP140-null cells show elevated energy expenditure and express high levels of the uncoupling protein 1 gene (Ucp1), carnitine palmitoyltransferase 1b, and the cell-death-inducing DFF45-like effector A. Conversely, all these changes are abrogated by the reexpression of RIP140. Analysis of the Ucp1 promoter showed RIP140 recruitment to a key enhancer element, demonstrating a direct role in repressing gene expression. Therefore, reduction in the levels of RIP140 or prevention of its recruitment to nuclear receptors may provide novel mechanisms for the control of energy expenditure in adipose cells.

scholarly journals Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

2015 ◽  
Vol 35 (23) ◽  
pp. 3934-3944 ◽  
Author(s):  
Kayla A. Martin ◽  
Matteo Cesaroni ◽  
Michael F. Denny ◽  
Lena N. Lupey ◽  
Italo Tempera
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Posttranslational Modifications ◽  
Target Genes ◽  
Global Gene Expression ◽  
Parp Inhibition ◽  
Direct Role ◽  
Polycomb Repressive Complex 2 ◽  
And Function

Posttranslational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of the genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the polycomb repressive complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2, which resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2 target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to the loss of the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2.

scholarly journals The role of epigenetic modifications in plant responses to stress

2021 ◽  
Vol 45 (1) ◽  
pp. 3-12
Author(s):  
Xuefeng Lu ◽  
Tae Hyun
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Current Knowledge ◽  
Epigenetic Modifications ◽  
Plant Responses ◽  
Daughter Cells ◽  
Non Coding Rnas ◽  
Covalent Modifications ◽  
Mitosis And Meiosis

Epigenetics is the study of hereditary changes in gene expression under the premise that the nucleotide sequence is not changed. Such hereditary changes mainly involve DNA methylation, histone modification, and chromatin remodeling. These covalent modifications play indispensable roles in regulating gene expression; DNA replication, recombination, and repair; and cell differentiation. Epigenetic modifications can be partially inherited by daughter cells during mitosis and meiosis and influenced by external factors, such as environmental stresses and supply deficits. In this review, we summarize the current knowledge regarding epigenetic factors, such as DNA methylation, histone acetylation, and regulation by non-coding RNAs, in the development and stress response of plants.

scholarly journals Stress-activated Genomic Expression Changes Serve a Preparative Role for Impending Stress in Yeast

2008 ◽  
Vol 19 (11) ◽  
pp. 4580-4587 ◽  
Author(s):  
David B. Berry ◽  
Audrey P. Gasch
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Single Dose ◽  
Stress Resistance ◽  
Yeast Cells ◽  
Specific Gene ◽  
Mild Stress ◽  
General Stress ◽  
Acquired Stress Resistance

Yeast cells respond to stress by mediating condition-specific gene expression changes and by mounting a common response to many stresses, called the environmental stress response (ESR). Giaever et al. previously revealed poor correlation between genes whose expression changes in response to acute stress and genes required to survive that stress, raising question about the role of stress-activated gene expression. Here we show that gene expression changes triggered by a single dose of stress are not required to survive that stimulus but rather serve a protective role against future stress. We characterized the increased resistance to severe stress in yeast preexposed to mild stress. This acquired stress resistance is dependent on protein synthesis during mild-stress treatment and requires the “general-stress” transcription factors Msn2p and/or Msn4p that regulate induction of many ESR genes. However, neither protein synthesis nor Msn2/4p is required for basal tolerance of a single dose of stress, despite the substantial expression changes triggered by each condition. Using microarrays, we show that Msn2p and Msn4p play nonredundant and condition-specific roles in gene-expression regulation, arguing against a generic general-stress function. This work highlights the importance of condition-specific responses in acquired stress resistance and provides new insights into the role of the ESR.

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