Higher Order Chromatin Structure, Proteins, c-AMP, Ions Modifications and Cell Cycle Progression: Experimental Results and Polyelectrolyte Theory

Cell Growth ◽  
1982 ◽  
pp. 487-520 ◽  
Author(s):  
C. Nicolini ◽  
A. Belmont
Keyword(s):  
Cell Cycle ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Higher Order ◽  
Experimental Results ◽  
Cycle Progression ◽  
Polyelectrolyte Theory

scholarly journals The Essential Cell Cycle Regulator Setd8 Drives Chromatin Condensation during Terminal Erythroid Maturation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1035-1035
Author(s):  
Jeffrey Malik ◽  
Jacquelyn Lillis ◽  
Michael Getman ◽  
Laurie A Steiner
Keyword(s):  
Cell Cycle ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Chromatin Condensation ◽  
Higher Order ◽  
S Phase ◽  
Cycle Progression ◽  
Cell Cycle Regulator ◽  
The Impact ◽  
Mitotic Chromatin

Abstract Chromatin condensation culminating in enucleation is a hallmark of erythropoiesis, however the mechanisms driving this process are incompletely understood. Setd8 is the sole enzyme that can mono-methylate histone H4, lysine 20 (H4K20me1) and is an important regulator of cell cycle progression, higher order chromatin structure, and genome stability. (Reviewed in Beck, Genes and Development, 2010) Setd8 and H4K20me1 are unique among epigenetic regulators in that their expression is dynamically regulated during the cell cycle. Setd8 expression peaks during G2/M, where it promotes mitotic chromatin condensation, and becomes undetectable during S-phase due to ubiquitin dependent destruction. (Oda, Mol Cell, 2010) The presence of H4K20me1 mirrors that of Setd8, peaking in G2/M, and reaching a nadir during S-phase due to removal by the histone demethylase PHF8. (Liu, Nature, 2010) Interestingly, Setd8 is expressed at levels 8- to 10- fold higher in CD71+ erythroblasts than in any other cell type, (Wu Genome Biology,2009) suggesting that it has an erythroid-specific function. We hypothesize that Setd8 drives chromatin condensation in maturing erythroblasts. In cell lines, forced accumulation of H4K20me1 during S-phase due to perturbation of either Setd8 or PHF8 results in pre-mitotic chromatin condensation (Centore Mol Cell 2010; Liu Nature 2010). We demonstrate that primary erythroblasts express Setd8 and accumulate H4K20me1 throughout the cell cycle, suggesting that Setd8 and H4K20me1 in promote chromatin condensation during terminal maturation. We further demonstrate that Setd8 is essential for erythropoiesis, with erythroid-specific Setd8 deletion resulting in profound anemia that is lethal by E12.5. The early onset of anemia indicates a defect in the primitive erythroid lineage, which emerges from the yolk sac at E8.5, and proliferates, matures, and enucleates in the circulation as a semi-synchronous cohort. (Kingsley, Blood, 2004) Detailed analyses of Setd8-null erythroblasts revealed severe defects in cell cycle progression, increased DNA content suggesting loss of genomic integrity, accumulation of DNA damage, and a modest increase in the rate of apoptosis. Global transcriptome analyses demonstrated that Setd8-null erythroblasts had activation of checkpoint genes such as CDKN1a and Gene Set Enrichment Analyses identified significant enrichment of cell cycle and p53 signaling pathways. Despite evidence of p53 activation, concomitant p53 deletion was not able to rescue the Set8-null phenotype, indicating that Setd8 has an essential role in promoting erythroid proliferation and survival that is independent of the p53 pathway. Consistent with our hypothesis that Setd8 drives chromatin condensation in maturing erythroblasts, the nuclear area of Setd8-null cells was nearly twice that of controls at E11.5 (119 and 69 um2, respectively p<0.0003). Transmission electron microscopy confirmed a profound defect in global chromatin condensation in the Setd8-null cells. Unexpectedly, heterochromatin was nearly absent from the Setd8-null cells, with the Setd8-null cells containing only a small amount of heterochromatin localized to the nuclear periphery. To determine the impact of Setd8 deletion on local chromatin structure, we performed ATAC-seq (Assay for Transposase Accessible Chromatin) on sorted populations of Setd8-null and control erythroblasts. Preliminary analyses of ATAC-seq data identified 364 ATAC peaks present in the Setd8-null cells but not in controls (p<0.001). Intriguingly, Gene Ontogeny analyses of the genes nearest to those regions was significant for multiple terms associated with higher order chromatin structure including "regulation of chromatin organization" and "positive regulation of histone deacetylation." Taken together, our results indicate that erythroblasts have adapted an essential cell cycle regulator to drive chromatin condensation during terminal maturation. Disclosures No relevant conflicts of interest to declare.

Effect of n-butyrate on cell cycle progression and in situ chromatin structure of L1210 cells

1981 ◽  
Vol 136 (2) ◽  
pp. 279-293 ◽  
Author(s):  
Zbigniew Darzynkiewicz ◽  
Frank Traganos ◽  
Shao-Bai Xue ◽  
Myron R. Melamed
Keyword(s):  
Cell Cycle ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
L1210 Cells

scholarly journals DNA in transcriptionally silent chromatin assumes a distinct topology that is sensitive to cell cycle progression.

1997 ◽  
Vol 17 (12) ◽  
pp. 7077-7087 ◽  
Author(s):  
X Bi ◽  
J R Broach
Keyword(s):  
Cell Cycle ◽  
Mating Type ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Type Locus ◽  
Cis Acting ◽  
Nucleosome Density ◽  
Superhelical Density ◽  
Insight Into

Transcriptionally silent regions of the Saccharomyces cerevisiae genome, the silent mating type loci and telomeres, represent the yeast equivalent of metazoan heterochromatin. To gain insight into the nature of silenced chromatin structure, we have examined the topology of DNA spanning the HML silent mating type locus by determining the superhelical density of mini-circles excised from HML (HML circles) by site-specific recombination. We observed that HML circles excised in a wild-type (SIR+) strain were more negatively supercoiled upon deproteinization than were the same circles excised in a sir- strain, in which silencing was abolished, even when HML alleles in which neither circle was transcriptionally competent were used. cis-acting sites flanking HML, called silencers, are required in the chromosome for establishment and inheritance of silencing. HML circles excised without silencers from cells arrested at any point in the cell cycle retained SIR-dependent differences in superhelical density. However, progression through the cell cycle converted SIR+ HML circles to a form resembling that of circles from sir- cells. This decay was not observed with circles carrying a silencer. These results establish that (i) DNA in transcriptionally silenced chromatin assumes a distinct topology reflecting a distinct organization of silenced versus active chromatin; (ii) the altered chromatin structure in silenced regions likely results from changes in packaging of individual nucleosomes, rather than changes in nucleosome density; and (iii) cell cycle progression disrupts the silenced chromatin structure, a process that is counteracted by silencers.

1955-P: GLP-1R Activation Attenuates Prostate Cancer Growth via Inhibiting Cell Cycle Progression

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1955-P
Author(s):  
TORU SHIGEOKA ◽  
TAKASHI NOMIYAMA ◽  
TAKAKO KAWANAMI ◽  
YURIKO HAMAGUCHI ◽  
TOMOKO TANAKA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cancer Growth ◽  
Cycle Progression
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