scholarly journals A viral histone-like protein exploits H1-HMGB1 antagonism for chromatin invasion

2020 ◽  
Author(s):  
Kelsey L Lynch ◽  
Mongoljin Bat-Erdene ◽  
Melanie R Dillon ◽  
Hannah C Lewis ◽  
Daphne C Avgousti
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Histone H1 ◽  
Linker Histone ◽  
Human Cells ◽  
Progeny Production ◽  
Cycle Progression ◽  
Linker Histone H1 ◽  
Viral Progeny ◽  
Host Chromatin

Virus infection necessarily requires redirecting cellular resources towards viral progeny production. Adenovirus successfully accomplishes this by usurping host chromatin through multiple approaches from redistributing histone modifications to globally altering chromatin composition. We previously showed that adenovirus histone-like protein VII sequesters the histone chaperone SET and the HMGB family of alarmins in host chromatin. HMGB1 has been shown to antagonize linker histone H1 binding to chromatin. Consistent with this antagonism, we find several H1 isoforms significantly chromatin-depleted in the presence of protein VII and accompanying HMGB proteins. Here, we use complementary systems in Saccharomyces cerevisiae and human cells to dissect the mechanism of chromatin invasion by adenovirus protein VII. In yeast, we find that protein VII binds chromatin and subsequently slows cell growth. Using yeast genetics, we demonstrate that loss of HMGB1 or SET homologs rescues this growth defect, indicating that these factors are required for the phenotype, while deletion of the linker histone H1 homolog exacerbates the defect. Strikingly, expression of human SET or HMGB1 in the corresponding mutant background restores the defects. We find that as a consequence of chromatin invasion, protein VII disrupts cell cycle progression such that cells accumulate in G2/M, both in yeast and diploid human cells. Moreover, we demonstrate that protein VII can impede the cell cycle in the presence of adenovirus E1A and E1B, two viral proteins well-established to override cell cycle checkpoints. Together, our results demonstrate that protein VII exploits H1-HMGB1 antagonism to invade chromatin and obstruct cell cycle progression, ensuring cellular resources are directed towards viral progeny production.

scholarly journals Linker histone H1 is present in centromeric chromatin of living human cells next to inner kinetochore proteins

2009 ◽  
Vol 37 (10) ◽  
pp. 3391-3406 ◽  
Author(s):  
S. Orthaus ◽  
K. Klement ◽  
N. Happel ◽  
C. Hoischen ◽  
S. Diekmann
Keyword(s):  
Histone H1 ◽  
Linker Histone ◽  
Human Cells ◽  
Centromeric Chromatin ◽  
Linker Histone H1

scholarly journals Ki-67 contributes to normal cell cycle progression and inactive X heterochromatin in p21 checkpoint-proficient human cells

2017 ◽  
Author(s):  
Xiaoming Sun ◽  
Aizhan Bizhanova ◽  
Timothy D. Matheson ◽  
Jun Yu ◽  
Lihua Julie Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Nuclear Lamina ◽  
Cell Types ◽  
S Phase ◽  
Human Cells ◽  
Cell Cycle Distribution ◽  
Ki 67 ◽  
Primary Fibroblast ◽  
Cycle Progression

AbstractKi-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive × (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.

scholarly journals Dynamics of sister chromatid resolution during cell cycle progression

2018 ◽  
Author(s):  
Rugile Stanyte ◽  
Johannes Nuebler ◽  
Claudia Blaukopf ◽  
Rudolf Hoefler ◽  
Roman Stocsits ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Sister Chromatid ◽  
Cell Cycle Progression ◽  
Human Cells ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Dividing Cells ◽  
G2 Phase ◽  
Almost All

Faithful genome transmission in dividing cells requires that the two copies of each chromosome’s DNA package into separate, but physically linked, sister chromatids. The linkage between sister chromatids is mediated by cohesin, yet where sister chromatids are linked and how they resolve during cell cycle progression has remained unclear. Here, we investigated sister chromatid organization in live human cells using dCas9-mEGFP labelling of endogenous genomic loci. We detected substantial sister locus separation during G2 phase, irrespective of the proximity to cohesin enrichment sites. Almost all sister loci separated within a few hours after their respective replication, and then rapidly equilibrated their average distances within dynamic chromatin polymers. Our findings explain why the topology of sister chromatid resolution in G2 largely reflects the DNA replication program. Further, these data suggest that cohesin enrichment sites are not persistent cohesive sites in human cells. Rather, cohesion might occur at variable genomic positions within the cell population.

scholarly journals A novel role for fanconi anemia (FA) pathway effector protein FANCD2 in cell cycle progression of untransformed primary human cells

Cell Cycle ◽  
2010 ◽  
Vol 9 (12) ◽  
pp. 2375-2388 ◽  
Author(s):  
Ihn Young Song ◽  
Laura R. Barkley ◽  
Tovah A. Day ◽  
Robert S. Weiss ◽  
Cyrus Vaziri
Keyword(s):  
Cell Cycle ◽  
Fanconi Anemia ◽  
Cell Cycle Progression ◽  
Human Cells ◽  
Effector Protein ◽  
Cycle Progression ◽  
Primary Human Cells

scholarly journals Ki-67 Contributes to Normal Cell Cycle Progression and Inactive X Heterochromatin in p21 Checkpoint-Proficient Human Cells

2017 ◽  
Vol 37 (17) ◽  
Author(s):  
Xiaoming Sun ◽  
Aizhan Bizhanova ◽  
Timothy D. Matheson ◽  
Jun Yu ◽  
Lihua Julie Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Nuclear Lamina ◽  
Cell Types ◽  
S Phase ◽  
Human Cells ◽  
Cell Cycle Distribution ◽  
Ki 67 ◽  
Primary Fibroblast ◽  
Cycle Progression

ABSTRACT The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by codepletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of the cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive X (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S-phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.

scholarly journals Human cells lacking CDC14A and CDC14B show differences in ciliogenesis but not in mitotic progression

2020 ◽  
pp. jcs.255950
Author(s):  
Patrick Partscht ◽  
Borhan Uddin ◽  
Elmar Schiebel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Mitotic Exit ◽  
Human Cells ◽  
Mitotic Progression ◽  
Cycle Progression ◽  
Double Deletion ◽  
Redundant Functions

Budding yeast Cdc14 phosphatase has a central role in mitotic exit and cytokinesis. Puzzlingly, a uniform picture for the three human CDC14 paralogues hCDC14A, B and C in cell cycle control has not emerged to date. Redundant functions between the three hCDC14 phosphatases could explain this unclear picture. To address the possibility of redundancy, we tested expression of hCDC14 and analysed cell cycle progression of cells with single- and double-deletion in hCDC14 genes. Our data suggest that hCDC14C is not expressed in human RPE1 cells excluding a function in this cell line. Single- and double-knockouts (KO) of hCDC14A and hCDC14B in RPE1 cells indicate that both phosphatases are not important for the timing of mitotic phases, cytokinesis and cell proliferation. However, cycling hCDC14A KO and hCDC14B KO cells show altered ciliogenesis compared to WT cells. The cilia of cycling hCDC14A KO cells are longer, whereas hCDC14B KO cilia are more frequent and disassemble faster. In conclusion, this study demonstrates that the cell cycle functions of CDC14 proteins are not conserved between yeast and human cells.

scholarly journals Dynamics of sister chromatid resolution during cell cycle progression

2018 ◽  
Vol 217 (6) ◽  
pp. 1985-2004 ◽  
Author(s):  
Rugile Stanyte ◽  
Johannes Nuebler ◽  
Claudia Blaukopf ◽  
Rudolf Hoefler ◽  
Roman Stocsits ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Sister Chromatid ◽  
Cell Cycle Progression ◽  
Human Cells ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Dividing Cells ◽  
G2 Phase ◽  
Almost All

Faithful genome transmission in dividing cells requires that the two copies of each chromosome’s DNA package into separate but physically linked sister chromatids. The linkage between sister chromatids is mediated by cohesin, yet where sister chromatids are linked and how they resolve during cell cycle progression has remained unclear. In this study, we investigated sister chromatid organization in live human cells using dCas9-mEGFP labeling of endogenous genomic loci. We detected substantial sister locus separation during G2 phase irrespective of the proximity to cohesin enrichment sites. Almost all sister loci separated within a few hours after their respective replication and then rapidly equilibrated their average distances within dynamic chromatin polymers. Our findings explain why the topology of sister chromatid resolution in G2 largely reflects the DNA replication program. Furthermore, these data suggest that cohesin enrichment sites are not persistent cohesive sites in human cells. Rather, cohesion might occur at variable genomic positions within the cell population.

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