scholarly journals Human ZNF312b oncogene is regulated by Sp1 binding to its promoter region through DNA demethylation and histone acetylation in gastric cancer

2011 ◽  
Vol 129 (9) ◽  
pp. 2124-2133 ◽  
Author(s):  
In-Sung Song ◽  
Ga-Hee Ha ◽  
Jeong-Min Kim ◽  
So-Young Jeong ◽  
Han-Chul Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Histone Acetylation ◽  
Promoter Region ◽  
Dna Demethylation

scholarly journals Unraveling the functional role of DNA methylation using targeted DNA demethylation by steric blockage of DNA methyltransferase with CRISPR/dCas9

2020 ◽  
Author(s):  
Daniel M. Sapozhnikov ◽  
Moshe Szyf
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Promoter Region ◽  
Dna Methyltransferase ◽  
Dna Demethylation ◽  
New Method ◽  
Inducible Promoters ◽  
Specific Targeting ◽  
Main Effect

AbstractAlthough associations between DNA methylation and gene expression were established four decades ago, the causal role of DNA methylation in gene expression remains unresolved. Different strategies to address this question were developed; however, all are confounded and fail to disentangle cause and effect. We developed here a highly effective new method using only deltaCas9(dCas9):gRNA site-specific targeting to physically block DNA methylation at specific targets in the absence of a confounding flexibly-tethered enzymatic activity, enabling examination of the role of DNA methylation per se in living cells. We show that the extensive induction of gene expression achieved by TET/dCas9-based targeting vectors is confounded by DNA methylation-independent activities, inflating the role of DNA methylation in the promoter region. Using our new method, we show that in several inducible promoters, the main effect of DNA methylation is silencing basal promoter activity. Thus, the effect of demethylation of the promoter region in these genes is small, while induction of gene expression by different inducers is large and DNA methylation independent. In contrast, targeting demethylation to the pathologically silenced FMR1 gene targets robust induction of gene expression. We also found that standard CRISPR/Cas9 knockout generates a broad unmethylated region around the deletion, which might confound interpretation of CRISPR/Cas9 gene depletion studies. In summary, this new method could be used to reveal the true extent, nature, and diverse contribution to gene regulation of DNA methylation at different regions.

scholarly journals lncRNA MIR22HG-Derived miR-22-5p Enhances the Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Through the Inhibition of HDAC2 Activity

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiao Jin ◽  
Hao Hu ◽  
Siqi Yan ◽  
Long Jin ◽  
Yuliang Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Promoter Region ◽  
Animal Experiments ◽  
Primary Hepatocellular Carcinoma ◽  
Acetylation Level ◽  
Expression Levels

BackgroundWith the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.MethodA microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation in vitro. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2′-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the in vivo effect of MIR22HG on the radiosensitivity of hepatoma.ResultsIrradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity via miR-22-5p in HCC.ConclusionInhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.

A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

2018 ◽  
Vol 27 (7) ◽  
pp. 822-828 ◽  
Author(s):  
Weizhi Wang ◽  
Mulong Du ◽  
Zheng Li ◽  
Lei Zhang ◽  
Qing Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Promoter Region ◽  
Genetic Variant

scholarly journals Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Ruiying Tong ◽  
Xian Wu ◽  
Ying Liu ◽  
Yang Liu ◽  
Jigang Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Colony Formation ◽  
Curcuma Longa ◽  
Mitochondrial Damage ◽  
Dna Demethylation ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
And Migration

Curcumin, a natural polyphenol antioxidant extracted from the root of turmeric (Curcuma longa), can induce apoptosis and DNA demethylation in several types of cancer cells. However, the mechanism of its anticancer potentials and DNA demethylation effects and the potential relationships between these outcomes have not been clearly elucidated. In the present study, the effects of curcumin on the proliferation, colony formation, and migration of human gastric cancer cells (hGCCs) were explored. Reactive oxygen species (ROS) levels, mitochondrial damage, DNA damage, and apoptosis of curcumin-treated hGCCs were analyzed. Changes in the expression of several genes related to DNA damage repair, the p53 pathway, cell cycle, and DNA methylation following curcumin treatment were also evaluated. We observed that curcumin inhibited the proliferation, colony formation, and migration of hGCCs in a dose- and time-dependent fashion. A high concentration of curcumin elevated ROS levels and triggered mitochondrial damage, DNA damage, and apoptosis of hGCCs. Further, curcumin-induced DNA demethylation of hGCCs was mediated by the damaged DNA repair-p53-p21/GADD45A-cyclin/CDK-Rb/E2F-DNMT1 axis. We propose that the anticancer effect of curcumin could largely be attributed to its prooxidative effect at high concentrations and ROS elevation in cancer cells. Moreover, we present a novel mechanism by which curcumin induces DNA demethylation of hGCCs, suggesting the need to further investigate the demethylation mechanisms of other DNA hypomethylating drugs.

scholarly journals Evaluation of MT Family Isoforms as Potential Biomarker for Predicting Progression and Prognosis in Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Mingfu Tong ◽  
Wenquan Lu ◽  
Hao Liu ◽  
Jian Wu ◽  
Mingzuo Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mrna Expression ◽  
Promoter Region ◽  
Gene Promoter ◽  
Distinct Type ◽  
Bioinformatic Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Wide Range ◽  
The Individual

Background. Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear. Methods. Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC. Results. Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients. Conclusion. MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.

scholarly journals Identification of High-Frequency Methylation Sites in RNF180 Promoter Region Affecting Expression and Their Relationship with Prognosis of Gastric Cancer

2020 ◽  
Vol Volume 12 ◽  
pp. 3389-3399
Author(s):  
Fang Han ◽  
Shuang Liu ◽  
Jingjing Jing ◽  
Hao Li ◽  
Yuan Yuan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Frequency ◽  
Promoter Region

Histone acetylation together with DNA demethylation empowers higher plasticity in adipocytes to differentiate into osteoblasts

Gene ◽  
2020 ◽  
Vol 733 ◽  
pp. 144274
Author(s):  
Young-Dan Cho ◽  
Bong-Su Kim ◽  
Woo-Jin Kim ◽  
Hyun-Jung Kim ◽  
Jeong-Hwa Baek ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Dna Demethylation

scholarly journals Histone acetylation recruits the SWR1 complex to regulate active DNA demethylation in Arabidopsis

2019 ◽  
Vol 116 (33) ◽  
pp. 16641-16650 ◽  
Author(s):  
Wen-Feng Nie ◽  
Mingguang Lei ◽  
Mingxuan Zhang ◽  
Kai Tang ◽  
Huan Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Conceptual Framework ◽  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Nuclear Protein ◽  
Dna Demethylation ◽  
Specific Target ◽  
Active Dna Demethylation ◽  
Chromatin Remodeling Complex ◽  
Genomic Regions

Active DNA demethylation is critical for controlling the DNA methylomes in plants and mammals. However, little is known about how DNA demethylases are recruited to target loci, and the involvement of chromatin marks in this process. Here, we identify 2 components of the SWR1 chromatin-remodeling complex, PIE1 and ARP6, as required for ROS1-mediated DNA demethylation, and discover 2 SWR1-associated bromodomain-containing proteins, AtMBD9 and nuclear protein X1 (NPX1). AtMBD9 and NPX1 recognize histone acetylation marks established by increased DNA methylation 1 (IDM1), a known regulator of DNA demethylation, redundantly facilitating H2A.Z deposition at IDM1 target loci. We show that at some genomic regions, H2A.Z and DNA methylation marks coexist, and H2A.Z physically interacts with ROS1 to regulate DNA demethylation and antisilencing. Our results unveil a mechanism through which DNA demethylases can be recruited to specific target loci exhibiting particular histone marks, providing a conceptual framework to understand how chromatin marks regulate DNA demethylation.

Role of histone acetylation in gastric cancer: implications of dietetic compounds and clinical perspectives

Epigenomics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 349-362 ◽  
Author(s):  
Danielle Q Calcagno ◽  
Fernanda Wisnieski ◽  
Elizangela R da Silva Mota ◽  
Stefanie B Maia de Sousa ◽  
Jéssica M Costa da Silva ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Histone Acetylation
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