scholarly journals Time-Course Transcriptome Study Reveals Mode of bZIP Transcription Factors on Light Exposure in Arabidopsis

2020 ◽  
Vol 21 (6) ◽  
pp. 1993 ◽  
Author(s):  
Yukio Kurihara ◽  
Yuko Makita ◽  
Haruka Shimohira ◽  
Minami Matsui
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Target Genes ◽  
Light Exposure ◽  
Expression Profiles ◽  
Red Light ◽  
Monochromatic Light ◽  
Regulation Of Gene Expression ◽  
Light Irradiation

The etiolation process, which occurs after germination, is terminated once light is perceived and then de-etiolation commences. During the de-etiolation period, monochromatic lights (blue, red and far-red) induce differences in gene expression profiles and plant behavior through their respective photoreceptors. ELONGATED HYPOCOTYL 5 (HY5), a bZIP-type transcription factor (TF), regulates gene expression in the de-etiolation process, and other bZIP TFs are also involved in this regulation. However, transcriptomic changes that occur in etiolated seedlings upon monochromatic light irradiation and the relationship with the bZIP TFs still remain to be elucidated. Here, we track changes in the transcriptome after exposure to white, blue, red and far-red light following darkness and reveal both shared and non-shared trends of transcriptomic change between the four kinds of light. Interestingly, after exposure to light, HY5 expression synchronized with those of the related bZIP TF genes, GBF2 and GBF3, rather than HY5 HOMOLOG (HYH). To speculate on the redundancy of target genes between the bZIP TFs, we inspected the genome-wide physical binding sites of homodimers of seven bZIP TFs, HY5, HYH, GBF1, GBF2, GBF3, GBF4 and EEL, using an in vitro binding assay. The results reveal large overlaps of target gene candidates, indicating a complicated regulatory literature among TFs. This work provides novel insight into understanding the regulation of gene expression of the plant response to monochromatic light irradiation.

Pan-cancer analysis on microRNA-mediated gene activation

2018 ◽  
Author(s):  
Hua Tan ◽  
Shan Huang ◽  
Zhigang Zhang ◽  
Xiaohua Qian ◽  
Peiqing Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Immune Cell ◽  
Critical Role ◽  
Mirna Gene ◽  
Regulation Of Gene Expression ◽  
The Cancer Genome Atlas ◽  
Positive Correlation ◽  
Positive Correlations

ABSTRACTWhile microRNAs (miRNAs) were widely considered to repress target genes at mRNA and/or protein levels, emerging evidence from in vitro experiments has shown that miRNAs can also activate gene expression in particular contexts. However, this counterintuitive observation has rarely been reported or interpreted in in vivo conditions. We systematically explored the positive correlation between miRNA and gene expressions and its potential implications in tumorigenesis, based on 8375 patient samples across 31 major human cancers from The Cancer Genome Atlas (TCGA). Results indicated that positive miRNA-gene correlations are surprisingly prevalent and consistent across cancer types, and show distinct patterns than negative correlations. The top-ranked positive correlations are significantly involved in the immune cell differentiation and cell membrane signaling related processes, and display strong power in stratifying patients in terms of survival rate, demonstrating their promising clinical relevance. Although intragenic miRNAs generally tend to co-express with their host genes, a substantial portion of miRNAs shows no obvious correlation with their host gene due to non-conservation. A miRNA can upregulate a gene by inhibiting its upstream suppressor, or shares transcription factors with that gene, both leading to positive correlation. The miRNA/gene sites associated with the top-ranked positive correlations are more likely to form super-enhancers compared to randomly chosen pairs, suggesting a potential epigenetics mechanism underlying the upregulation. Wet-lab experiments revealed that positive correlations partially remain in the in vitro condition. Our study provides the field with new perspectives on the critical role of miRNA in gene regulation and novel insights regarding the complex mechanisms underlying miRNA functions, and reveals the clinical significance of the potential positive regulation of gene expression by miRNA.

scholarly journals Selective silencing rather than targeted activation of gene expression underlies fate choice in human hematopoietic stem cells

2020 ◽  
Author(s):  
R Parmentier ◽  
A Moussy ◽  
S Chantalat ◽  
L Racine ◽  
R Sudharshan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Target Genes ◽  
Expression Profiles ◽  
Second Phase ◽  
Gene Promoters ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Cell Subpopulations

AbstractWhen human cord blood derived CD34+ cells are induced to differentiate in vitro, they undergo rapid and dynamic morphological and molecular transformation that are critical for the fate commitment. Using ATAC-seq and single-cell RNA sequencing, we detected two phases of this process. In the first phase, we observed that a rapid and widespread chromatin opening - that makes most of the gene promoters in the genome accessible - precedes a global upregulation of gene transcription and a concomitant increase in the cell-to-cell variability of gene expression. The second phase is marked by a slow chromatin closure that precedes an overall downregulation of gene transcription and the emergence of coherent expression profiles that characterize distinct cell subpopulations. We further showed that the accessibility of promoters has a crucial effect on whether transcription factor changes will lead to alterations in the expression of their target genes. Our observations are consistent with a model based on the spontaneous probabilistic organization of the cellular process of fate commitment.

scholarly journals Utility of MicroRNAs and siRNAs in Cervical Carcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sacnite del Mar Díaz-González ◽  
Jessica Deas ◽  
Odelia Benítez-Boijseauneau ◽  
Claudia Gómez-Cerón ◽  
Victor Hugo Bermúdez-Morales ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Viral Gene ◽  
Cervical Carcinogenesis ◽  
Transmitted Infection ◽  
Therapy Strategy ◽  
Cell Proliferation Inhibition

MicroRNAs and siRNAs belong to a family of small noncoding RNAs which bind through partial sequence complementarity to 3′-UTR regions of mRNA from target genes, resulting in the regulation of gene expression. MicroRNAs have become an attractive target for genetic and pharmacological modulation due to the critical function of their target proteins in several signaling pathways, and their expression profiles have been found to be altered in various cancers. A promising technology platform for selective silencing of cell and/or viral gene expression using siRNAs is currently in development. Cervical cancer is the most common cancer in women in the developing world and sexually transmitted infection with HPV is the cause of this malignancy. Therefore, a cascade of abnormal events is induced during cervical carcinogenesis, including the induction of genomic instability, reprogramming of cellular metabolic pathways, deregulation of cell proliferation, inhibition of apoptotic mechanisms, disruption of cell cycle control mechanisms, and alteration of gene expression. Thus, in the present review article, we highlight new research on microRNA expression profiles which may be utilized as biomarkers for cervical cancer. Furthermore, we discuss selective silencing of HPV E6 and E7 with siRNAs which represents a potential gene therapy strategy against cervical cancer.

scholarly journals Molecular signature of anastasis for reversal of apoptosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 43 ◽  
Author(s):  
Ho Man Tang ◽  
C. Conover Talbot Jr ◽  
Ming Chiu Fung ◽  
Ho Lam Tang
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Cancer Cell Line ◽  
Molecular Signature ◽  
Cell Recovery ◽  
Therapeutic Implications

Anastasis (Greek for "rising to life") is a cell recovery phenomenon that rescues dying cells from the brink of cell death. We recently discovered anastasis to occur after the execution-stage of apoptosis in vitro and in vivo. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis – the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-cell survival, anti-oxidation, cell cycle arrest, histone modification, DNA-damage and stress-inducible responses, and at delayed times, angiogenesis and cell migration. Validation with RT-PCR confirmed similar changes in the human liver cancer cell line, HepG2, during anastasis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.

scholarly journals Targeting the CALCB/RAMP1-axis inhibits growth of Ewing sarcoma

2018 ◽  
Author(s):  
Marlene Dallmayer ◽  
Jing Li ◽  
Shunya Ohmura ◽  
Rebeca Alba-Rubio ◽  
Michaela C. Baldauf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ewing Sarcoma ◽  
Time Course ◽  
Target Genes ◽  
Enhancer Activity ◽  
Gene Expression Microarrays ◽  
Active Enhancer ◽  
Expression Microarrays

ABSTRACTEwing sarcoma (EwS) is an aggressive cancer caused by chromosomal translocations generating fusions of theEWSR1gene withETStranscription factors (in 85%FLI1). EWSR1-FLI1 induces gene expression via binding to enhancer-like GGAA-microsatellites, whose activity increases with the number of consecutive GGAA-repeats.Herein, we investigate the role of the secretory neuropeptide CALCB (calcitonin related polypeptide β) in EwS, which signals via the CGRP-(calcitonin gene-related peptide) receptor complex, containing RAMP1 (receptor activity modifying protein 1) as crucial part for receptor specificity. Analysis of 2,678 gene expression microarrays comprising 50 tumor entities and 71 normal tissue types revealed thatCALCBis specifically and highly overexpressed in EwS. Time-course knockdown experiments showed thatCALCBexpression is tightly linked to that ofEWSR1-FLI1. Consistently, gene set enrichment analyses of genes whose expression in primary EwS is correlated to that ofCALCBindicated that it is co-expressed with other EWSR1-FLI1 target genes and associated with signatures involved in stemness and proliferation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data for EWSR1-FLI1 and histone marks from EwS cells demonstrated that EWSR1-FLI1 binds to a GGAA-microsatellite close toCALCB, which exhibits characteristics of an active enhancer. Reporter assays confirmed the strong EWSR1-FLI1- and length-dependent enhancer activity of this GGAA-microsatellite. Mass-spectrometry analyses of supernatants of EwS cell cultures demonstrated that CALCB is secreted by EwS cells. While short-term RNA interference-mediatedCALCBknockdown had no effect on proliferation and clonogenic growth of EwS cellsin vitro, its long-term knockdown decreased EwS growthin vitroandin vivo. Similarly, knockdown ofRAMP1reduced clonogenic/spheroidal growth and tumorigenicity, and small-molecule inhibitors directed against the CGRP-receptor comprising RAMP1 reduced growth of EwS.Collectively, our findings suggest thatCALCBis a direct EWSR1-FLI1 target and that targeting the CALCB/RAMP1-axis may offer a new therapeutic strategy for inhibition of EwS growth.

Identification of Target Genes for the Tumor Suppressor RIZ1 Using Gene Expression Profiling.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4351-4351
Author(s):  
Wei-Feng Dong ◽  
Naoto Takahashi ◽  
Matthew N. Bainbridge ◽  
Andrea R. Hull ◽  
Stuart A. Scott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Gene Expression Profiling ◽  
Cell Line ◽  
Expression Profiling ◽  
Target Genes ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Gene Expression Profiles ◽  
Cmv Promoter

Abstract RIZ1 (PRDM2) is a tumor suppressor gene on 1p36 that frequently undergoes deletion, rearrangements, and loss of heterozygosity in a broad spectrum of tumors. RIZ1 is a member of the nuclear protein methyltransferase superfamily involved in chromatin remodeling. RIZ1 contains a ~130 amino acid conserved domain (PR or SET) that is important in chromatin-mediated regulation of gene expression and in the development of cancer. RIZ1 methylates Histone H3 on K9 and this activity may play a role in transcription repression as H3-K9 methylation is known to be associated with repression. Aberrant activities or mistargeting of chromatin modifying activities are proving to have unexpected links to cancer. We and others have shown that RIZ1 expression is down regulated in human leukemias and in the human erythroleukemia cell line K562. Expression of RIZ1 in K562 reduced proliferation, increased apoptosis, and promoted erythroid differentiation. To understand how RIZ1’s DNA binding, methyltransferase, and transcription repressor functions are related to its tumor suppressor activity it is necessary to characterize RIZ1 target genes. We used DNA microarrays to globally monitor how RIZ1 affects gene expression profiles. We constructed a K562 cell line with RIZ1 stably integrated under the control of a CMV promoter and analyzed the gene expression profiles of K652 and K562 + RIZ1 using a 42K Stanford human gene microarray. By comparing the gene expression profiles of these cell lines, we identified potential RIZ1 gene targets that are up and down regulated in the presence of RIZ1. In total, we identified 5 upregulated genes and 20 down regulated genes using significance analysis of microarrays (SAM) and standard deviation filter analysis of the gene expression data. RIZ1-mediated changes in gene expression profiling indicate that RIZ1 is potentially involved in the regulation and connection of the IGF-1 (IGF-1, IGFBP2) and integrin (LMS1) pathways, and in the activation of the TGF-β (SPARC) pathway. The genes perturbed by RIZ1 expression suggest that the tumor suppressor properties of RIZ1 arise from its control of proliferation, apoptosis and differentiation using these pathways. Finally, we observed an overrepresentation of the SP-1 transcription factor binding sites in genes that are upregulated in the absence of RIZ1. This correlates with the ability of RIZ1 to recognize SP1 sequences.

Bmi1 Is Essential for Leukemic Reprogramming of Myeloid Progenitor Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1423-1423
Author(s):  
Jin Yuan ◽  
Masahiro Takeuchi ◽  
Hideyuki Oguro ◽  
Masamitsu Negishi ◽  
Hitoshi Ichikawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Target Genes ◽  
Expression Profiles ◽  
Myelogenous Leukemia ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Myeloid Progenitor ◽  
Immortalized Cells

Abstract Abstract 1423 Poster Board I-446 The polycomb group (PcG) protein Bmi1 plays an essential role in the maintenance of self-renewing hematopoietic stem cells (HSCs). Derepressed p16Ink4a and p19Arf are tightly associated with a loss of self-renewing capacity of HSCs in Bmi1-deficient mice. Deletion of both Ink4a and Arf genes substantially restores the self-renewal capacity of Bmi1−/− HSCs. Thus, Bmi1 maintains HSCs by acting as a critical failsafe against the p16Ink4a- and p19Arf-dependent senescence pathway. Meanwhile, Bmi1 was originally identified as a collaborating oncogene in the induction of lymphoma and was subsequently reported to be overexpressed in various human cancers including leukemia. Recent studies have demonstrated that PcG proteins bind to multiple regions of the genome and regulate a bunch of target genes. Therefore, we asked whether Bmi1 is essential for leukemic stem cells (LSCs) and tried to identify critical target genes for Bmi1 other than Ink4a and Arf in leukemia. We expressed the MLL-AF9 leukemic fusion gene in purified Lin−Sca-1−c-Kit+CD34+FcγRII/ IIIhi granulocyte/macrophage progenitors (GMPs) from wild-type, Bmi1−/−, Ink4a-Arf−/−, and Bmi1−/−Ink4a-Arf−/− mice and performed in vitro myeloid progenitor replating assay. GMPs from 4 different genetic backgrounds were all immortalized in vitro, although Bmi1-deficient cells showed a slightly decreased replating efficiency. We then infused the immortalized cells into lethally irradiated recipient mice. Mice infused with wild-type and Ink4a-Arf−/− cells developed acute myelogenous leukemia (AML) at 30 to 60 days after infusion. Mice infused with Bmi1−/− cells did not develop leukemia at all. While a significant portion of mice infused with Bmi1−/−Ink4a-Arf−/− cells developed AML, although they took much longer time compared to those mice infused with wild-type and Ink4a-Arf−/− cells. These results indicate that as in HSCs, the Ink4a /Arf locus is one of the major targets for Bmi1 in leukemogenesis. In order to find unknown targets of Bmi1 in LSCs, we compared gene expression profiles of purified c-KithiFcRγII/IIIhiCD34+ cells from Ink4a-Arf−/− and Bmi1−/−Ink4a-Arf−/− immortalized cells. We found that the loss of Bmi1 did not affect the induction of MLL-AF9 target gene expression. By contrast, a number of genes were derepressed in the absence of Bmi1. Among these, Tbx15, a transcriptional co-repressor gene, appeared to be regulated by Bmi1 and a potential tumor suppressor gene in the development of leukemia. Of interest, the majority of derepressed target genes in transformed Bmi1−/−Ink4a-Arf−/− cells, including Tbx15, remained unchanged by re-expression of Bmi1. Correspondingly, re-introduction of Bmi1 to transformed Bmi1−/−Ink4a-Arf−/− cells failed to rescue their compromised leukemogenic activity in vivo. Our findings suggest that Bmi1 is required for faithful epigenetic reprogramming of myeloid progenitors into LSCs by leukemic fusions and contributes to establish LSC-specific transcriptional profiles to confer full leukemogenic activity on LSCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cytotoxic and Transcriptomic Effects in Avian Hepatocytes Exposed to a Complex Mixture from Air Samples, and Their Relation to the Organic Flame Retardant Signature

Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 324
Author(s):  
Kelsey Ha ◽  
Pu Xia ◽  
Doug Crump ◽  
Amandeep Saini ◽  
Tom Harner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Flame Retardants ◽  
Target Genes ◽  
Expression Profiles ◽  
Complex Mixture ◽  
Gene Expression Profiles ◽  
P Value ◽  
Pls Modeling

Assessing complex environmental mixtures and their effects is challenging. In this study, we evaluate the utility of an avian in vitro screening approach to determine the effects of passive air sampler extracts collected from different global megacities on cytotoxicity and gene expression. Concentrations of a suite of organic flame retardants (OFRs) were quantified in extracts from a total of 19 megacities/major cities in an earlier study, and levels were highly variable across sites. Chicken embryonic hepatocytes were exposed to serial dilutions of extracts from the 19 cities for 24 h. Cell viability results indicate a high level of variability in cytotoxicity, with extracts from Toronto, Canada, having the lowest LC50 value. Partial least squares (PLS) regression analysis was used to estimate LC50 values from OFR concentrations. PLS modeling of OFRs was moderately predictive of LC50 (p-value = 0.0003, r2 = 0.66, slope = 0.76, when comparing predicted LC50 to actual values), although only after one outlier city was removed from the analysis. A chicken ToxChip PCR array, comprising 43 target genes, was used to determine effects on gene expression, and similar to results for cell viability, gene expression profiles were highly variable among the megacities. PLS modeling was used to determine if gene expression was related to the OFR profiles of the extracts. Weak relationships to the ToxChip expression profiles could be detected for only three of the 35 OFRs (indicated by regression slopes between 0.6 and 0.5 when comparing predicted to actual OFR concentrations). While this in vitro approach shows promise in terms of evaluating effects of complex mixtures, we also identified several limitations that, if addressed in future studies, might improve its performance.

scholarly journals In VitroGene Expression Dissected: Chemostat Surgery forMycobacterium tuberculosis

2002 ◽  
Vol 3 (4) ◽  
pp. 345-347 ◽  
Author(s):  
Brian W. James ◽  
Joanna Bacon ◽  
Tobias Hampshire ◽  
Kim Morley ◽  
Philip D. Marsh
Keyword(s):  
Gene Expression ◽  
Culture System ◽  
Time Course ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Multiple Time ◽  
Unique Approach ◽  
Highly Correlated

A unique approach, combining defined and reproduciblein vitromodels with DNA microarrays, has been developed to study environmental modulation of mycobacterial gene expression. The gene expression profiles of samples ofMycobacterium tuberculosis, from independent chemostat cultures grown under defined and reproducible conditions, were found to be highly correlated. This approach is now being used to study the effect of relevant stimuli, such as limited oxygen availability, on mycobacterial gene expression. A modification of the chemostat culture system, enabling largevolume controlled batch culture, has been developed to study starvation survival. Cultures ofM. tuberculosishave been maintained under nutrient-starved conditions for extended periods, with106–107bacilli surviving in a culturable state after 100 days. The design of the culture system has made it possible to control the environment and collect multiple time-course samples to study patterns of gene expression. These studies demonstrate that it is possible to perform long-term studies and obtain reproducible expression data using controlled and definedin vitromodels.

scholarly journals Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

2010 ◽  
Vol 17 (3) ◽  
pp. 809-822 ◽  
Author(s):  
Louise Maymann Rasmussen ◽  
Klaus Stensgaard Frederiksen ◽  
Nanni Din ◽  
Elisabeth Galsgaard ◽  
Leif Christensen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Pituitary Hormone

The pituitary hormone prolactin (PRL) plays an important role in mammary gland development. It was also suggested to contribute to breast cancer progression. In vivo data strongly supported a crucial role of PRL in promoting tumour growth; however, PRL demonstrated only a weak, if any, pro-proliferative effect on cancer cells in vitro. Several recent studies indicated that PRL action in vivo may be influenced by the hormonal milieu, e.g. other growth factors such as 17β-oestradiol (E2). Here, we explored the potential interplay between PRL and E2 in regulation of gene expression and cell growth. PRL alone induced either a weak or no proliferative response of T47D and BT-483 cells respectively, while it drastically enhanced cell proliferation in E2-stimulated cultures. Affymetrix microarray analysis revealed 12 genes to be regulated by E2, while 57 genes were regulated by PRL in T47D cells. Most of the PRL-regulated genes (42/57) were not previously described as PRL target genes, e.g. WT1 and IER3. One hundred and five genes were found to be regulated upon PRL/E2 co-treatment: highest up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3, SOCS3, WT1 and AREG. PRL and E2 synergised to regulate EGR3, while multiple genes were regulated additively. These data show a novel interplay between PRL and E2 to modulate gene regulation in breast cancer cells.

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