Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines

2013 ◽  
Vol 36 (5) ◽  
pp. 351-362 ◽  
Author(s):  
Floor A.M. Duijkers ◽  
Renee X. de Menezes ◽  
Inès J. Goossens-Beumer ◽  
Dominique J.P.M. Stumpel ◽  
Pieter Admiraal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Drug Combination ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Epigenetic Drug ◽  
Altered Gene

Abstract A19: Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines

2014 ◽  
Author(s):  
Max M. van Noesel ◽  
Floor A M Duijkers ◽  
Renee X. de Menezes ◽  
Dominique J. P. M. Stumpel ◽  
Pieter Admiraal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Drug Combination ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Epigenetic Drug ◽  
Altered Gene

scholarly journals Modeling human prostate cancer progression in vitro

2018 ◽  
Vol 40 (7) ◽  
pp. 893-902 ◽  
Author(s):  
Teresa T Liu ◽  
Jonathan A Ewald ◽  
Emily A Ricke ◽  
Robert Bell ◽  
Colin Collins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Prostate ◽  
Molecular Characteristics ◽  
Prostate Cancer Progression ◽  
Altered Gene Expression ◽  
Unique Model ◽  
Altered Gene

Abstract Detailed mechanisms involved in prostate cancer (CaP) development and progression are not well understood. Current experimental models used to study CaP are not well suited to address this issue. Previously, we have described the hormonal progression of non-tumorigenic human prostate epithelial cells (BPH1) into malignant cells via tissue recombination. Here, we describe a method to derive human cell lines from distinct stages of CaP that parallel cellular, genetic and epigenetic changes found in patients with cancers. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. Using diverse analytical strategies, we show that the BCaP model reproduces molecular characteristics of CaP in human patients. Furthermore, we demonstrate that BCaP cells have altered gene expression of shared pathways with human and transgenic mouse CaP data, as well as, increasing genomic instability with TMPRSS2–ERG fusion in advanced tumor cells. Together, these cell lines represent a unique model of human CaP progression providing a novel tool that will allow the discovery and experimental validation of mechanisms regulating human CaP development and progression. This BPH1-derived Cancer Progression (BCaP) model represents different stages of cancer. The BCaP model reproduces molecular characteristics of prostate cancer. The cells have altered gene expression with TMPRSS2-ERG fusion representing a unique model for prostate cancer progression.

scholarly journals Silent crickets reveal the genomic footprint of recent adaptive trait loss

2018 ◽  
Author(s):  
Sonia Pascoal ◽  
Judith E. Risse ◽  
Xiao Zhang ◽  
Mark Blaxter ◽  
Timothee Cezard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Loss ◽  
Sexual Signal ◽  
Adaptive Trait ◽  
Field Crickets ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
High Density Linkage Map ◽  
Mutational Effect

Secondary trait loss is widespread and has profound consequences, from generating diversity to driving adaptation. Sexual trait loss is particularly common. Its genomic impact is challenging to reconstruct because most reversals occurred in the distant evolutionary past and must be inferred indirectly, and questions remain about the extent of disruption caused by pleiotropy, altered gene expression and loss of homeostasis. We tested the genomic signature of recent sexual signal loss in Hawaiian field crickets, Teleogryllus oceanicus. Song loss is controlled by a sex-linked Mendelian locus, flatwing, which feminises male wings by erasing sound-producing veins. This variant spread rapidly under pressure from an eavesdropping parasitoid fly. We sequenced, assembled and annotated the T. oceanicus genome, produced a high-density linkage map, and localised flatwing on the X chromosome. We characterised pleiotropic effects of flatwing, including changes in embryonic gene expression and alteration of another sexual signal, chemical pheromones. Song loss is associated with pleiotropy, hitchhiking and genome-wide regulatory disruption which feminises flatwing male pheromones. The footprint of recent adaptive trait loss illustrates R. A. Fisher's influential prediction that variants with large mutational effect sizes can invade genomes during the earliest stages of adaptation to extreme pressures, despite having severely disruptive genomic consequences.

199 IN VITRO-DEVELOPED BOVINE BLASTOCYSTS ARE MARKED WITH ABERRANT HYPER- AND HYPO-METHYLATED GENOMIC REGIONS

2015 ◽  
Vol 27 (1) ◽  
pp. 190
Author(s):  
D. Salilew-Wondim ◽  
M. Hoelker ◽  
U. Besenfelder ◽  
V. Havlicek ◽  
F. Rings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Proximal Promoter ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
Genomic Regions

Most often, in vitro produced embryos display poor quality and altered gene expression patterns compared to their in vivo counterparts. Aberrant DNA methylation occurring during in vitro embryo development is believed to be one of the multifaceted factors which may cause altered gene expression and poor embryo quality. Here, we investigated the genome-wide DNA methylation patterns of in vitro derived embryos using the recently developed Bovine EmbryoGENE Methylation Platform (BEGMP) array (Shojaei Saadi et al. BMC Genomics 2014 15, 451. doi: 10.1186/1471-2164-15-451) to unravel the aberrantly methylated genomic region in in vitro developed embryos. For this, in vitro and in vivo produced blastocysts were produced and used for genome-wide DNA methylation analysis. In vitro blastocysts were produced from oocytes retrieved from ovaries collected from the local abattoir and matured, fertilized, and cultured in vitro using SOF media. The in vivo blastocysts were produced by superovulation and AI of Simmental heifers followed by uterine flushing. Genomic DNA (gDNA) was then isolated from four replicates (each 10 blastocysts) of in vivo and in vitro derived blastocysts using Allprep DNA/RNA micro kit (Qiagen, Valencia, CA, USA) and the gDNA was then fragmented using the MseI enzyme. Following this, MseLig21 and MseLig were ligated to the MseI-digested genomic fragments in the presence of Ligase enzyme. Methyl-sensitive enzymes, HpaII, AciI, and Hinp1I, were used to cleave unmethlayted genomic regions within the MseI-MseI region of the fragmented DNA. The gDNA was subjected to two rounds of ligation-mediated polymerase chain reaction (LM-PCR) amplification. After removal of the adapters, the amplified gDNA samples from in vivo or in vitro groups were labelled either Cy-3 or Cy-5 dyes in dye-swap design using ULS Fluorescent gDNA labelling kit (Kreatech Biotechnology BV, Amsterdam, The Netherlands). Hybridization was performed for 40 h at 65°C. Slides were scanned using Agilent's High-Resolution C Scanner (Agilent Technologies Inc., Santa Clara, CA, USA) and features were extracted with Agilent's Feature Extraction software (Agilent Technologies Inc.). The results have shown that from a total of 414 566 probes harboured by the BEGMP array, 248 453 and 253 147 probes were detected in in vitro and in vivo derived blastocysts, respectively. Data analysis using the linear modelling for microarray (LIMMA) package and R software (The R Project for Statistical Computing, Vienna, Austria) revealed a total of 3434 differentially methylated regions (DMRs; Fold change ≥1.5, P-value <0.05), of which 42 and 58% were hyper- and hypo-methylated, respectively, in in vitro derived blastocysts compared to their in vivo counterparts. The DMRs were found to be localised in the intronic, exonic, promoter, proximal promoter, and distal promoter, and some of the probes did not have nearby genes. In addition, 10.8% of the DMRs were found to be stretched in short, long, or intermediate CpG islands. Thus, this study demonstrated genome-wide dysregulation in the epigenome landscape of in vitro-derived embryos by the time they reach to the blastocysts stage.

Altered gene expression in lymphoblastoid cell lines after subculture

2018 ◽  
Vol 54 (7) ◽  
pp. 523-527 ◽  
Author(s):  
Michihiro Toritsuka ◽  
Manabu Makinodan ◽  
Takahira Yamauchi ◽  
Yasunori Yamashita ◽  
Daisuke Ikawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Lymphoblastoid Cell Lines ◽  
Altered Gene Expression ◽  
Altered Gene

Genome wide profiling of altered gene expression in the neocortex of Alzheimer's disease

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Michelle G. Tan ◽  
Wei-Ting Chua ◽  
Margaret M. Esiri ◽  
A. David Smith ◽  
Harry V. Vinters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene

Molecular and Microscopic Analysis of Altered Gene Expression in Transgenic and Gene Targeted Mice

1996 ◽  
Vol 54 ◽  
pp. 12-13
Author(s):  
W. K. Jones ◽  
J. Robbins
Keyword(s):  
Gene Expression ◽  
Pulmonary Veins ◽  
Microscopic Analysis ◽  
Mouse Tissue ◽  
Adult Heart ◽  
Heavy Chains ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Pulmonary Myocardium

Two myosin heavy chains (MyHC) are expressed in the mammalian heart and are differentially regulated during development. In the mouse, the α-MyHC is expressed constitutively in the atrium. At birth, the β-MyHC is downregulated and replaced by the α-MyHC, which is the sole cardiac MyHC isoform in the adult heart. We have employed transgenic and gene-targeting methodologies to study the regulation of cardiac MyHC gene expression and the functional and developmental consequences of altered α-MyHC expression in the mouse.We previously characterized an α-MyHC promoter capable of driving tissue-specific and developmentally correct expression of a CAT (chloramphenicol acetyltransferase) marker in the mouse. Tissue surveys detected a small amount of CAT activity in the lung (Fig. 1a). The results of in situ hybridization analyses indicated that the pattern of CAT transcript in the adult heart (Fig. 1b, top panel) is the same as that of α-MyHC (Fig. 1b, lower panel). The α-MyHC gene is expressed in a layer of cardiac muscle (pulmonary myocardium) associated with the pulmonary veins (Fig. 1c). These studies extend our understanding of α-MyHC expression and delimit a third cardiac compartment.

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