scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

2019 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Transformation ◽  
Regulatory Elements ◽  
Histone Variant ◽  
List Type ◽  
Cycle Arrest ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Canonical Histone

SummaryReplication-dependent canonical histone messenger RNAs (mRNAs) do not terminate with a poly(A) tail at the 3’ end. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA. The addition of a poly(A) tail to the H3.1 mRNA caused transformation of human cells in vitro, but the underlying mechanisms are unknown. Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein level, resulting in depletion of histone variant H3.3 at active promoters, enhancers, and insulator regions through its displacement. Cells underwent transcriptional deregulation, G2/M cell cycle arrest, chromosome aneuploidy and aberrations. Furthermore, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation, suggesting that H3.3 displacement might be central to tumorigenic effects of polyadenylated H3.1 mRNA. Our study provides novel insights into the importance of proper histone stoichiometry in maintaining genome integrity.HighlightsPolyadenylation of canonical histone H3.1 mRNA promotes tumor formation in nude miceHistone variant H3.3 is displaced from critical gene regulatory elements by overexpression of polyadenylated H3.1 mRNAIncreased polyadenylated H3.1 mRNA causes abnormal transcription, cell cycle arrest, and chromosomal instabilityArsenic induces polyadenylation of H3.1 mRNA in vivo

Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation.

1988 ◽  
Vol 7 (6) ◽  
pp. 1635-1645 ◽  
Author(s):  
A. J. Ridley ◽  
H. F. Paterson ◽  
M. Noble ◽  
H. Land
Keyword(s):  
Cell Cycle ◽  
Schwann Cell ◽  
Cell Cycle Arrest ◽  
Cell Transformation ◽  
Cycle Arrest

scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

2019 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Regulatory Elements ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

scholarly journals Cellular Iron Depletion and the Mechanisms Involved in the Iron-dependent Regulation of the Growth Arrest and DNA Damage Family of Genes

2011 ◽  
Vol 286 (41) ◽  
pp. 35396-35406 ◽  
Author(s):  
Federica Saletta ◽  
Yohan Suryo Rahmanto ◽  
Aritee R. Siafakas ◽  
Des R. Richardson
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Family Members ◽  
Growth Arrest ◽  
Regulatory Elements ◽  
Mrna Levels ◽  
Iron Depletion ◽  
Cellular Iron ◽  
Cycle Arrest

Iron plays a crucial part in proliferation while iron deficiency results in G1/S arrest, DNA damage, and apoptosis. However, the precise role of iron in cell cycle control remains unclear. We showed that iron depletion using the iron chelators, desferrioxamine (DFO), or 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311), increased the mRNA levels of the growth arrest and DNA damage 45α gene, GADD45α (Darnell, G. and Richardson, D. R. (1999) Blood 94, 781–792). In this study, we examined the effect of iron depletion on up-regulating GADD family members involved in growth control, including cell cycle arrest, apoptosis, and DNA repair, making them therapeutic targets for tumor suppression. We showed the GADD family members were up-regulated by cellular iron depletion. Further, up-regulation of GADD45α after iron deprivation was independent of hypoxia-inducible factor-1α (HIF-1α), octamer-1 (Oct-1), p53 and early growth response 1 (Egr1). We then analyzed the regulatory elements responsible for iron depletion-mediated regulation of GADD45α and identified the specific transcription factor/s involved. This region was within −117 bp and −81 bp relative to the start codon where the consensus sequences of three transcription factors are located: the CCAAT-binding factor/nuclear factor-Y (NF-Y), the stabilizing molecule v-MYB and the enhancer, CCAAT enhancer-binding protein (CEBPα). Mutation analysis, shRNA studies, Western blotting, and electrophoretic mobility shift assays led to the identification of NF-Y in the transcriptional up-regulation of GADD45α after iron depletion. Furthermore, like GADD45α, NF-YA was up-regulated after iron chelation and down-regulated by iron supplementation. These results are important for understanding the mechanisms of iron depletion-mediated cell cycle arrest, DNA damage repair, and apoptosis.

scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101518 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Regulatory Elements ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

PPAR-γ ligands induce G1 cell cycle arrest and reduce ornithine decarboxylase activity of human Barrett's adenocarcinoma cells

2001 ◽  
Vol 120 (5) ◽  
pp. A415-A415
Author(s):  
T TAKASHIMA ◽  
Y FUJIWARA ◽  
K HIGUCHI ◽  
T ARAKAWA ◽  
Y YANO ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Ornithine Decarboxylase Activity ◽  
Ppar Γ ◽  
Cycle Arrest ◽  
Adenocarcinoma Cells ◽  
Barrett’S Adenocarcinoma ◽  
G1 Cell Cycle Arrest

Helicobacter pylori induces cell cycle arrest of T-lymphocytes

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Gerhard ◽  
C Schmees ◽  
R Rad ◽  
P Voland ◽  
T Treptau ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Helicobacter Pylori ◽  
T Lymphocytes ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

Mechanisms of interferon-induced cell cycle arrest

10.2741/a527 ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. d479-487 ◽  
Author(s):  
Dan Grandér
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest
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