scholarly journals Epigenetic displacement of HP1 from heterochromatin by HIV-1 Vpr causes premature sister chromatid separation

2011 ◽  
Vol 194 (5) ◽  
pp. 721-735 ◽  
Author(s):  
Mari Shimura ◽  
Yusuke Toyoda ◽  
Kenta Iijima ◽  
Masanobu Kinomoto ◽  
Kenzo Tokunaga ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosomes ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Viral Pathogen ◽  
Chromatid Cohesion ◽  
Epigenetic Disruption ◽  
First Time ◽  
Order Structures ◽  
Hiv 1

Although pericentromeric heterochromatin is essential for chromosome segregation, its role in humans remains controversial. Dissecting the function of HIV-1–encoded Vpr, we unraveled important properties of heterochromatin during chromosome segregation. In Vpr-expressing cells, hRad21, hSgo1, and hMis12, which are crucial for proper chromosome segregation, were displaced from the centromeres of mitotic chromosomes, resulting in premature chromatid separation (PCS). Interestingly, Vpr displaced heterochromatin protein 1-α (HP1-α) and HP1-γ from chromatin. RNA interference (RNAi) experiments revealed that down-regulation of HP1-α and/or HP1-γ induced PCS, concomitant with the displacement of hRad21. Notably, Vpr stimulated the acetylation of histone H3, whereas p300 RNAi attenuated the Vpr-induced displacement of HP1-α and PCS. Furthermore, Vpr bound to p300 that was present in insoluble regions of the nucleus, suggesting that Vpr aberrantly recruits the histone acetyltransferase activity of p300 to chromatin, displaces HP1-α, and causes chromatid cohesion defects. Our study reveals for the first time centromere cohesion impairment resulting from epigenetic disruption of higher-order structures of heterochromatin by a viral pathogen.

scholarly journals Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B

2020 ◽  
Vol 48 (12) ◽  
pp. 6583-6596
Author(s):  
Akiko Fujimura ◽  
Yuki Hayashi ◽  
Kazashi Kato ◽  
Yuichiro Kogure ◽  
Mutsuro Kameyama ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Protein Complex ◽  
Metaphase Plate ◽  
Nucleolar Protein ◽  
Aurora B ◽  
Mitotic Progression ◽  
Mitotic Chromosomes ◽  
Nucleolar Proteins ◽  
Chromatid Cohesion ◽  
Wd Repeat

Abstract The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.

Phosphorylation of histone H3 by Haspin regulates chromosome alignment and segregation during mitosis in maize

2020 ◽  
Author(s):  
Yang Liu ◽  
Chunhui Wang ◽  
Handong Su ◽  
James A Birchler ◽  
Fangpu Han
Keyword(s):  
Chromosome Segregation ◽  
Histone H3 ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Factor B ◽  
Microtubule Attachment ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
Mitosis And Meiosis

Abstract In human cells, Haspin-mediated histone H3 threonine 3 (H3T3) phosphorylation promotes centromeric localization of the chromosomal passenger complex, thereby ensuring proper kinetochore–microtubule attachment. Haspin also binds to PDS5 cohesin-associated factor B (Pds5B), antagonizing the Wings apart-like protein homolog (Wapl)–Pds5B interaction and thus preventing Wapl from releasing centromeric cohesion during mitosis. However, the role of Haspin in plant chromosome segregation is not well understood. Here, we show that in maize (Zea mays) mitotic cells, ZmHaspin localized to the centromere during metaphase and anaphase, whereas it localized to the telomeres during meiosis. These results suggest that ZmHaspin plays different roles during mitosis and meiosis. Knockout of ZmHaspin led to decreased H3T3 phosphorylation and histone H3 serine 10 phosphorylation, and defects in chromosome alignment and segregation in mitosis. These lines of evidence suggest that Haspin regulates chromosome segregation in plants via the mechanism described for humans, namely, H3T3 phosphorylation. Plant Haspin proteins lack the RTYGA and PxVxL motifs needed to bind Pds5B and heterochromatin protein 1, and no obvious cohesion defects were detected in ZmHaspin knockout plants. Taken together, these results highlight the conserved but slightly different roles of Haspin proteins in cell division in plants and in animals.

scholarly journals Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells

2011 ◽  
Vol 22 (8) ◽  
pp. 1181-1190 ◽  
Author(s):  
Jungseog Kang ◽  
Jaideep Chaudhary ◽  
Hui Dong ◽  
Soonjoung Kim ◽  
Chad A. Brautigam ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Human Cells ◽  
Structural Studies ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Chromatid Cohesion ◽  
A Subunit ◽  
Chromosome Passenger Complex ◽  
Chromo Shadow Domain

Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres.

scholarly journals Heterochromatin protein 1 distribution during development and during the cell cycle in Drosophila embryos

1995 ◽  
Vol 108 (4) ◽  
pp. 1407-1418 ◽  
Author(s):  
R. Kellum ◽  
J.W. Raff ◽  
B.M. Alberts
Keyword(s):  
Cell Cycle ◽  
Polytene Chromosomes ◽  
Apical Surface ◽  
Gaga Factor ◽  
Mitotic Chromosomes ◽  
Heterochromatin Protein 1 ◽  
Dapi Staining ◽  
Heterochromatin Protein ◽  
Nuclear Cycle ◽  
Drosophila Embryos

Heterochromatin protein 1 (HP1) was initially discovered as a protein that is associated with the heterochromatin at the chromocenter of polytene chromosomes in Drosophila larval salivary glands. In this paper we investigate the localization of heterochromatin protein 1 in the diploid nuclei of Drosophila embryos. We focus on its association with the interphase heterochromatin in fixed embryos before and during cycle 14, the developmental time at which heterochromatin becomes most conspicuous, and also follow its localization during mitosis. The GAGA transcription factor was recently shown to be localized at sequences within alpha-heterochromatin in pre-cycle 14 embryos, and an antibody against this protein serves as a convenient marker for these sequences. We find an enrichment of heterochromatin protein 1 in the intensely DAPI-staining regions near the apical surface of nuclear cycle 10 embryos. At this stage GAGA factor is localized into punctate structures in this same region. This enrichment for HP1 is markedly increased during nuclear cycle 14. Surprisingly, whereas GAGA factor retains its association with the heterochromatin throughout the cell cycle, a significant fraction of HP1 is dispersed throughout the spindle around the segregating chromosomes during mitosis. This dispersed pool of heterochromatin protein 1 was observed during mitosis in both early and late Drosophila embryos and in an analysis of a bacterially produced 6x histidine-heterochromatin protein 1 fusion protein injected into living Drosophila embryos. When Drosophila tissue culture cells were prepared by a method which removes soluble protein and avoids fixation of the mitotic chromosomes, an enrichment for heterochromatin protein 1 in the heterochromatin of the chromosomes was discovered also.

scholarly journals FACT mediates cohesin function on chromatin

2019 ◽  
Author(s):  
Jonay Garcia-Luis ◽  
Luciana Lazar-Stefanita ◽  
Pilar Gutierrez-Escribano ◽  
Agnes Thierry ◽  
Alicia García ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Genome Architecture ◽  
Genome Organisation ◽  
Metaphase Chromosomes ◽  
Chromatid Cohesion ◽  
Loop Domains ◽  
Order Structures ◽  
Chromosome Organisation

AbstractCohesin is a key regulator of genome architecture with roles in sister chromatid cohesion 1,2 and the organisation of higher-order structures during interphase 3 and mitosis 4,5. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes 6-8. Here we show that cohesin role in chromosome organisation requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin-dependent compartmentalization of chromosomes into loop domains.

Heterochromatin protein 1 is required for correct chromosome segregation in Drosophila embryos

1995 ◽  
Vol 108 (4) ◽  
pp. 1419-1431 ◽  
Author(s):  
R. Kellum ◽  
B.M. Alberts
Keyword(s):  
Chromosome Segregation ◽  
Position Effect ◽  
Chromosome Morphology ◽  
Chromosome Condensation ◽  
Centromeric Heterochromatin ◽  
Position Effect Variegation ◽  
Loss Of Function ◽  
Heterochromatin Protein 1 ◽  
Gene Encoding ◽  
Heterochromatin Protein

Heterochromatin protein 1 is associated with centromeric heterochromatin in Drosophila, mice, and humans. Loss of function mutations in the gene encoding heterochromatin protein 1 in Drosophila, Suppressor of variegation2-5, decrease the mosaic repression observed for euchromatic genes that have been juxtaposed to centromeric heterochromatin. These heterochromatin protein 1 mutations not only suppress this position-effect variegation, but also cause recessive embryonic lethality. In this study, we analyze the latter phenotype in the hope of gaining insight into heterochromatin function. In our analyses of four alleles of Suppressor of variegation2-5, the lethality was found to be associated with defects in chromosome morphology and segregation. While some of these defects are seen throughout embryonic development, both the frequency and severity of the defects are greatest between cycles 10 and 14 when zygotic transcription of the Suppressor of variegation2-5 gene apparently begins. By this time in development, heterochromatin protein 1 levels are diminished by four-fold in a quarter of the embryos produced by parents that are both heterozygous for a null allele (Suppressor of variegation2-5(05)). In a live analysis of the phenotype, we find prophase to be lengthened by more than two-fold in Suppressor of variegation2-5(05) mutant embryos with subsequent defects in chromosome segregation. The elongated prophase suggests that the segregation phenotype is a consequence of defects in events that occur during prophase, either in chromosome condensation or kinetochore assembly or function. Immunostaining with an antibody against a centromerespecific antigen indicates that the kinetochores of most chromosomes are functional. The immunostaining results are more consistent with defects in chromosome condensation being responsible for the segregation phenotype.

scholarly journals Histone Hyperacetylation in Mitosis Prevents Sister Chromatid Separation and Produces Chromosome Segregation Defects

2003 ◽  
Vol 14 (9) ◽  
pp. 3821-3833 ◽  
Author(s):  
Daniela Cimini ◽  
Marta Mattiuzzo ◽  
Liliana Torosantucci ◽  
Francesca Degrassi
Keyword(s):  
Sister Chromatid ◽  
Histone Deacetylases ◽  
Mitotic Checkpoint ◽  
Chromosome Condensation ◽  
Histone Deacetylation ◽  
Centromeric Heterochromatin ◽  
Chromatin Conformation ◽  
Mitotic Chromosomes ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein

Posttranslational modifications of core histones contribute to driving changes in chromatin conformation and compaction. Herein, we investigated the role of histone deacetylation on the mitotic process by inhibiting histone deacetylases shortly before mitosis in human primary fibroblasts. Cells entering mitosis with hyperacetylated histones displayed altered chromatin conformation associated with decreased reactivity to the anti-Ser 10 phospho H3 antibody, increased recruitment of protein phosphatase 1-δ on mitotic chromosomes, and depletion of heterochromatin protein 1 from the centromeric heterochromatin. Inhibition of histone deacetylation before mitosis produced defective chromosome condensation and impaired mitotic progression in living cells, suggesting that improper chromosome condensation may induce mitotic checkpoint activation. In situ hybridization analysis on anaphase cells demonstrated the presence of chromatin bridges, which were caused by persisting cohesion along sister chromatid arms after centromere separation. Thus, the presence of hyperacetylated chromatin during mitosis impairs proper chromosome condensation during the pre-anaphase stages, resulting in poor sister chromatid resolution. Lagging chromosomes consisting of single or paired sisters were also induced by the presence of hyperacetylated histones, indicating that the less constrained centromeric organization associated with heterochromatin protein 1 depletion may promote the attachment of kinetochores to microtubules coming from both poles.

scholarly journals Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 805-813 ◽  
Author(s):  
Edward S Davis ◽  
Lucia Wille ◽  
Barry A Chestnut ◽  
Penny L Sadler ◽  
Diane C Shakes ◽  
...  
Keyword(s):  
Rna Interference ◽  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Anaphase Promoting Complex ◽  
Genetic Screens ◽  
Chromatid Cohesion ◽  
Interference Studies ◽  
Meiosis I

Abstract Two genes, originally identified in genetic screens for Caenorhabditis elegans mutants that arrest in metaphase of meiosis I, prove to encode subunits of the anaphase-promoting complex or cyclosome (APC/C). RNA interference studies reveal that these and other APC/C subunits are essential for the segregation of chromosomal homologs during meiosis I. Further, chromosome segregation during meiosis I requires APC/C functions in addition to the release of sister chromatid cohesion.

scholarly journals Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 953-964 ◽  
Author(s):  
D P Moore ◽  
W Y Miyazaki ◽  
J E Tomkiel ◽  
T L Orr-Weaver
Keyword(s):  
Cell Death ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Aberrant Chromosome ◽  
Chromatid Cohesion ◽  
Meiotic Nondisjunction ◽  
Lethal Allele ◽  
Meiosis I

Abstract We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.

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