scholarly journals Molecular mechanisms underlying ochratoxin A-induced genotoxicity: global gene expression analysis suggests induction of DNA double-strand breaks and cell cycle progression

2013 ◽  
Vol 38 (1) ◽  
pp. 57-69 ◽  
Author(s):  
Daisuke Hibi ◽  
Aki Kijima ◽  
Ken Kuroda ◽  
Yuta Suzuki ◽  
Yuji Ishii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle Progression ◽  
Gene Expression Analysis ◽  
Molecular Mechanisms ◽  
Global Gene Expression ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Cycle Progression ◽  
Strand Breaks ◽  
Global Gene Expression Analysis

scholarly journals Brg1 Enables Rapid Growth of the Early Embryo by Suppressing Genes That Regulate Apoptosis and Cell Growth Arrest

2016 ◽  
Vol 36 (15) ◽  
pp. 1990-2010 ◽  
Author(s):  
Ajeet P. Singh ◽  
Julie F. Foley ◽  
Mark Rubino ◽  
Michael C. Boyle ◽  
Arpit Tandon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Regulatory Region ◽  
Global Gene Expression ◽  
Early Embryo ◽  
Open Chromatin ◽  
Cycle Progression ◽  
Cell Growth Arrest ◽  
Global Gene Expression Analysis

SWI/SNF (switching/sucrose nonfermenting)-dependent chromatin remodeling establishes coordinated gene expression programs during development, yet important functional details remain to be elucidated. We show that the Brg1 (Brahma-related gene 1; Smarca4) ATPase is globally expressed at high levels during postimplantation development and its conditional ablation, beginning at gastrulation, results in increased apoptosis, growth retardation, and, ultimately, embryonic death. Global gene expression analysis revealed that genes upregulated inRosa26CreERT2;Brg1flox/floxembryos (here referred to asBrg1d/dembryos to describe embryos with deletion of theBrg1flox/floxalleles) negatively regulate cell cycle progression and cell growth. In addition, the p53 (Trp53) protein, which is virtually undetectable in early wild-type embryos, accumulated in theBrg1d/dembryos and activated the p53-dependent pathways. Using P19 cells, we show that Brg1 and CHD4 (chromodomain helicase DNA binding protein 4) coordinate to control target gene expression. Both proteins physically interact and show a substantial overlap of binding sites at chromatin-accessible regions adjacent to genes differentially expressed in theBrg1d/dembryos. Specifically, Brg1 deficiency results in reduced levels of the repressive histone H3 lysine K27 trimethylation (H3K27me3) histone mark and an increase in the amount of open chromatin at the regulatory region of thep53andp21(Cdkn1a) genes. These results provide insights into the mechanisms by which Brg1 functions, which is in part via the p53 program, to constrain gene expression and facilitate rapid embryonic growth.

scholarly journals Sustained CHK2 activity, but not ATM activity, is critical to maintain a G1 arrest after DNA damage in untransformed cells

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Iraia García-Santisteban ◽  
Alba Llopis ◽  
Lenno Krenning ◽  
Jon Vallejo-Rodríguez ◽  
Bram van den Broek ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Cycle Progression ◽  
Double Strand Breaks ◽  
G1 Arrest ◽  
Dna Double Strand Breaks ◽  
Independent Manner ◽  
Cycle Progression ◽  
Strand Breaks ◽  
G1 Checkpoint ◽  
The Impact

Abstract Background The G1 checkpoint is a critical regulator of genomic stability in untransformed cells, preventing cell cycle progression after DNA damage. DNA double-strand breaks (DSBs) recruit and activate ATM, a kinase which in turn activates the CHK2 kinase to establish G1 arrest. While the onset of G1 arrest is well understood, the specific role that ATM and CHK2 play in regulating G1 checkpoint maintenance remains poorly characterized. Results Here we examine the impact of ATM and CHK2 activities on G1 checkpoint maintenance in untransformed cells after DNA damage caused by DSBs. We show that ATM becomes dispensable for G1 checkpoint maintenance as early as 1 h after DSB induction. In contrast, CHK2 kinase activity is necessary to maintain the G1 arrest, independently of ATM, ATR, and DNA-PKcs, implying that the G1 arrest is maintained in a lesion-independent manner. Sustained CHK2 activity is achieved through auto-activation and its acute inhibition enables cells to abrogate the G1-checkpoint and enter into S-phase. Accordingly, we show that CHK2 activity is lost in cells that recover from the G1 arrest, pointing to the involvement of a phosphatase with fast turnover. Conclusion Our data indicate that G1 checkpoint maintenance relies on CHK2 and that its negative regulation is crucial for G1 checkpoint recovery after DSB induction.

scholarly journals Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 46 ◽  
Author(s):  
Yi-Sheng Sun ◽  
Zhang-Nv Yang ◽  
Fang Xu ◽  
Chen Chen ◽  
Hang-Jing Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Global Gene Expression ◽  
Solid Foundation ◽  
Differential Gene ◽  
Global Gene Expression Analysis ◽  
Upregulated Genes

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two most important pathogens of hand, foot, and mouth disease (HFMD). However, the neuropathogenesis of EV71 and CVA16 has not been elucidated. In our previous study, we established gerbils as a useful model for both EV71 and CVA16 infection. In this work, we used RNA-seq technology to analyze the global gene expression of the brainstem of EV71- and CVA16-infected gerbils. We found that 3434 genes were upregulated while 916 genes were downregulated in EV71-infected gerbils. In CVA16-infected gerbils, 1039 genes were upregulated, and 299 genes were downregulated. We also found significant dysregulation of cytokines, such as IP-10 and CXCL9, in the brainstem of gerbils. The expression levels of 10 of the most upregulated genes were confirmed by real-time RT-PCR, and the upregulated tendency of most genes was in accordance with the differential gene expression (DGE) results. Our work provided global gene expression analysis of virus-infected gerbils and laid a solid foundation for elucidating the neuropathogenesis mechanisms of EV71 and CVA16.

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