scholarly journals Transcriptional landscape of cell lines and their tissues of origin

2016 ◽  
Author(s):  
Camila M. Lopes-Ramos ◽  
Joseph N. Paulson ◽  
Cho-Yi Chen ◽  
Marieke L. Kuijjer ◽  
Maud Fagny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
List Type ◽  
Cell Cycle Genes ◽  
Barr Virus ◽  
Network Analyses ◽  
Regulatory Processes

SummaryCell lines are an indispensable tool in biomedical research and often used as surrogates for tissues. An important question is how well a cell line’s transcriptional and regulatory processes reflect those of its tissue of origin. We analyzed RNA-Seq data from GTEx for 127 paired Epstein-Barr virus transformed lymphoblastoid cell lines and whole blood samples; and 244 paired fibroblast cell lines and skin biopsies. A combination of gene expression and network analyses shows that while cell lines carry the expression signatures of their primary tissues, albeit at reduced levels, they also exhibit changes in their patterns of transcription factor regulation. Cell cycle genes are over-expressed in cell lines compared to primary tissue, and they have a reduction of repressive transcription factor targeting. Our results provide insight into the expression and regulatory alterations observed in cell lines and suggest that these changes should be considered when using cell lines as models.HighlightsCell lines differ from their source tissues in gene expression and regulationDistinct cell lines share altered patterns of cell cycle regulationCell cycle genes are less strongly targeted by repressive TFs in cell linesCell lines share expression with their source tissue, but at reduced levels

scholarly journals MUTE Directly Orchestrates Cell State Switch and the Single Symmetric Division to Create Stomata

2018 ◽  
Author(s):  
Soon-Ki Han ◽  
Xingyun Qi ◽  
Kei Sugihara ◽  
Jonathan H. Dang ◽  
Takaho A. Endo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Division ◽  
List Type ◽  
Transcriptional Repressors ◽  
Potent Inducer ◽  
Feed Forward ◽  
Feed Forward Loop ◽  
Symmetric Division ◽  
Cell Cycle Genes

SUMMARYPrecise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing the single division event remains unclear. Here we report the complete inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by its sister bHLH, SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, and their transcriptional repressors, FAMA and FOUR LIPS. The architecture of the regulatory network initiated by MUTE represents an Incoherent Type 1 Feed-Forward Loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to the tightly-restricted, robust pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.HighlightsComplete inventories of gene expression in stomatal differentiation state are elucidatedMUTE switches stomatal patterning program initiated by its sister bHLH, SPEECHLESSMUTE directly induces cell-cycle genes and their direct transcriptional repressorsIncoherent feed-forward loop by MUTE ensures the single division of a stomatal precursor

scholarly journals TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

2018 ◽  
Author(s):  
Roberto Ferrari ◽  
Lara Isabel de Llobet Cucalon ◽  
Chiara Di Vona ◽  
François Le Dilly ◽  
Enrique Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Histone Acetylation ◽  
Cancer Biology ◽  
Repetitive Elements ◽  
Large Set ◽  
Alu Elements ◽  
Cell Cycle Genes ◽  
Chromatin Looping

Summary paragraphThe mammalian genome is shaped by the expansion of repetitive elements that provide new regulatory networks for coordinated control of gene expression1 and genome folding2–4. Alu elements (AEs) are selectively retained close to the transcription start site of genes5, show protoenhancer functions6, correlate with the level of chromatin interactions7 and are recognized by transcription factor III (TFIIIC)8, but the relevance of all this is not clear. Here we report regulatory mechanisms that unveil a central role of AEs and TFIIIC in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of pre-marked AEs near cell cycle genes recruit TFIIIC to alter their chromatin accessibility via TFIIIC-mediated acetylation of histone H3 Lysine-18 (H3K18). This facilitates AEs contact with distant CTCF sites near other cell cycle genes promoters, which also become hyperacetylated at H3K18. These changes ensure basal transcription of crucial cell cycle genes, and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor adjusts 3D genome folding and gene expression. We anticipate that expansion of several families of repetitive elements during evolution might have served to generate new genomic cis-regulatory circuits enabling the coordinated regulation of a large set of genes relevant for cellular stress survival. As growth factor withdrawal is a situation relevant in cancer biology, our study identifies TFIIIC as a new potential target for clinical intervention.

Bcl-2 protein localizes to the chromosomes of mitotic nuclei and is correlated with the cell cycle in cultured epithelial cell lines

1994 ◽  
Vol 107 (2) ◽  
pp. 363-371
Author(s):  
Q.L. Lu ◽  
A.M. Hanby ◽  
M.A. Nasser Hajibagheri ◽  
S.E. Gschmeissner ◽  
P.J. Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Cytoplasmic Localization ◽  
Human Epithelial Cell ◽  
Daughter Cells ◽  
Epithelial Cell Lines ◽  
Cell Immortalization

bcl-2 gene expression confers a survival advantage by preventing cells from entering apoptosis. In contrast to the previously described cytoplasmic localization of Bcl-2 in epithelial cells in vivo, in this study we have demonstrated, in a series of human epithelial cell lines, that Bcl-2 also localizes to mitotic nuclei. Both immunocytochemical and immunoelectron microscopical examinations localize this protein to nuclei and in particular to chromosomes. Nuclear Bcl-2 expression in these cell lines is correlated with the cell cycle. There is relatively strong expression during mitosis, most intense during prophase and metaphase, declining in telophase and then the protein becomes undetectable soon after separation of the two daughter cells. The expression and distribution of Bcl-2 is influenced by treatment with excessive thymidine. These results indicate that Bcl-2 may protect the cells from apoptosis occurring during mitosis and suggest a possible role for the protein in cell immortalization.

scholarly journals Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals

2013 ◽  
Vol 45 (19) ◽  
pp. 907-916
Author(s):  
Liwen Zhang ◽  
Dennis A. Simpson ◽  
Cynthia L. Innes ◽  
Jeff Chou ◽  
Pierre R. Bushel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Checkpoint ◽  
G2 Checkpoint ◽  
P53 Signaling ◽  
Normal Individuals ◽  
Gene Expression Signatures ◽  
Cycle Checkpoint ◽  
Atm Cell

Ataxia telangiectasia (AT) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia-mutated gene ( ATM). AT carriers with one mutant ATM allele are usually not severely affected although they carry an increased risk of developing cancer. There has not been an easy and reliable diagnostic method to identify AT carriers. Cell cycle checkpoint functions upon ionizing radiation (IR)-induced DNA damage and gene expression signatures were analyzed in the current study to test for differential responses in human lymphoblastoid cell lines with different ATM genotypes. While both dose- and time-dependent G1 and G2 checkpoint functions were highly attenuated in ATM−/− cell lines, these functions were preserved in ATM+/− cell lines equivalent to ATM+/+ cell lines. However, gene expression signatures at both baseline (consisting of 203 probes) and post-IR treatment (consisting of 126 probes) were able to distinguish ATM+/− cell lines from ATM+/+ and ATM−/− cell lines. Gene ontology (GO) and pathway analysis of the genes in the baseline signature indicate that ATM function-related categories, DNA metabolism, cell cycle, cell death control, and the p53 signaling pathway, were overrepresented. The same analyses of the genes in the IR-responsive signature revealed that biological categories including response to DNA damage stimulus, p53 signaling, and cell cycle pathways were overrepresented, which again confirmed involvement of ATM functions. The results indicate that AT carriers who have unaffected G1 and G2 checkpoint functions can be distinguished from normal individuals and AT patients by expression signatures of genes related to ATM functions.

scholarly journals Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated withMelicope ptelefolialeaf extract reveals transcriptome profiles exhibiting anticancer activity

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5203 ◽  
Author(s):  
Mohammad Faujul Kabir ◽  
Johari Mohd Ali ◽  
Onn Haji Hashim
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Replication ◽  
Cell Lines ◽  
Microarray Data ◽  
Expression Profiling ◽  
Cell Cycle Progression ◽  
Anticancer Activities ◽  
Microarray Gene Expression ◽  
Cycle Progression

BackgroundWe have previously reported anticancer activities ofMelicope ptelefolia(MP) leaf extracts on four different cancer cell lines. However, the underlying mechanisms of actions have yet to be deciphered. In the present study, the anticancer activity of MP hexane extract (MP-HX) on colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines was characterized through microarray gene expression profiling.MethodsHCT116 and HepG2 cells were treated with MP-HX for 24 hr. Total RNA was extracted from the cells and used for transcriptome profiling using Applied Biosystem GeneChip™ Human Gene 2.0 ST Array. Gene expression data was analysed using an Applied Biosystems Expression Console and Transcriptome Analysis Console software. Pathway enrichment analyses was performed using Ingenuity Pathway Analysis (IPA) software. The microarray data was validated by profiling the expression of 17 genes through quantitative reverse transcription PCR (RT-qPCR).ResultsMP-HX induced differential expression of 1,290 and 1,325 genes in HCT116 and HepG2 cells, respectively (microarray data fold change, MA_FC ≥ ±2.0). The direction of gene expression change for the 17 genes assayed through RT-qPCR agree with the microarray data. In both cell lines, MP-HX modulated the expression of many genes in directions that support antiproliferative activity. IPA software analyses revealed MP-HX modulated canonical pathways, networks and biological processes that are associated with cell cycle, DNA replication, cellular growth and cell proliferation. In both cell lines, upregulation of genes which promote apoptosis, cell cycle arrest and growth inhibition were observed, while genes that are typically overexpressed in diverse human cancers or those that promoted cell cycle progression, DNA replication and cellular proliferation were downregulated. Some of the genes upregulated by MP-HX include pro-apoptotic genes (DDIT3, BBC3, JUN), cell cycle arresting (CDKN1A, CDKN2B), growth arrest/repair (TP53, GADD45A) and metastasis suppression (NDRG1). MP-HX downregulated the expression of genes that could promote anti-apoptotic effect, cell cycle progression, tumor development and progression, which include BIRC5, CCNA2, CCNB1, CCNB2, CCNE2, CDK1/2/6, GINS2, HELLS, MCM2/10 PLK1, RRM2 and SKP2. It is interesting to note that all six top-ranked genes proposed to be cancer-associated (PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2) were downregulated by MP-HX in both cell lines.DiscussionThe present study showed that the anticancer activities of MP-HX are exerted through its actions on genes regulating apoptosis, cell proliferation, DNA replication and cell cycle progression. These findings further project the potential use of MP as a nutraceutical agent for cancer therapeutics.

scholarly journals Radiosensitization Effect of Nedaplatin on Nasopharyngeal Carcinoma Cells in Different Status of Epstein-Barr Virus Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Li Yin ◽  
Jing Wu ◽  
Jianfeng Wu ◽  
Jinjun Ye ◽  
Xuesong Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Cycle Arrest ◽  
M Phase ◽  
Epstein Barr ◽  
Mts Assay

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0–100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.

scholarly journals Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines

2006 ◽  
Vol 39 (1) ◽  
Author(s):  
ÁNGELA D ARMENDÁRIZ ◽  
FELIPE OLIVARES ◽  
RODRIGO PULGAR ◽  
ALEX LOGUINOV ◽  
VERÓNICA CAMBIAZO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Cell Lines ◽  
Expression Profiling ◽  
Fibroblast Cell ◽  
Wild Type ◽  
Fibroblast Cell Lines

scholarly journals Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7035 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Joël Baguet ◽  
Roxane Chalard ◽  
Bariza Blanquier ◽  
Lilia Brinza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factor Sp1 ◽  
Cell Cycle Inhibition
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