scholarly journals Transcriptional Profiling and Dynamical Regulation Analysis Identify Potential Kernel Target Genes of SCYL1-BP1 in HEK293T Cells

2014 ◽  
Vol 37 (9) ◽  
pp. 691-698
Author(s):  
Yang Wang ◽  
Xiaomei Chen ◽  
Xiaojing Chen ◽  
Qilong Chen ◽  
Keke Huo
Keyword(s):  
Target Genes ◽  
Transcriptional Profiling ◽  
Potential Kernel

scholarly journals Transcriptional Profiling Analysis of the Global Regulator NorG, a GntR-Like Protein of Staphylococcus aureus

2011 ◽  
Vol 193 (22) ◽  
pp. 6207-6214 ◽  
Author(s):  
Q. C. Truong-Bolduc ◽  
P. M. Dunman ◽  
T. Eidem ◽  
D. C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Target Genes ◽  
Efflux Pump ◽  
Transcriptional Profiling ◽  
Fold Increase ◽  
Regulatory Function ◽  
Drug Transporter ◽  
Content Type ◽  
Global Regulators ◽  
Inorganic Ion

The GntR-like protein NorG has been shown to affectStaphylococcus aureusgenes involved in resistance to quinolones and β-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional-profiling assays usingS. aureusRN6390 and its isogenicnorG::catmutant. Our data showed that NorG positively affected the transcription of global regulatorsmgrA,arlS, andsarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold) genes. TheS. aureuspredicted MmpL protein showed 53% homology with the MmpL lipid transporter ofMycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA ofStaphylococcus hominis. Two pump genes most negatively affected by NorG were the NorC (4-fold) and AbcA (6-fold) genes. Other categories of genes, such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time reverse transcription (RT)-PCR assays formgrA,arlS,sarZ,norB,norC,abcA,mmpL, andbcrA-like were carried out to verify microarray data and showed the same level of up- or downregulation by NorG. ThenorGmutant showed a 2-fold increase in resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression ofnorCon a plasmid. These data indicate that NorG has broad regulatory function inS. aureus.

scholarly journals Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome

Blood ◽  
2018 ◽  
Vol 132 (23) ◽  
pp. 2470-2483 ◽  
Author(s):  
Shiro Tara ◽  
Yusuke Isshiki ◽  
Yaeko Nakajima-Takagi ◽  
Motohiko Oshima ◽  
Kazumasa Aoyama ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Target Genes ◽  
Myeloproliferative Neoplasms ◽  
Lymphoblastic Leukemia ◽  
Transcriptional Profiling ◽  
Hoxa Cluster ◽  
Carboxyl Terminal ◽  
Regulator Genes ◽  
The Impact ◽  
P53 Target Genes

Abstract BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (BcorΔE4/y) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (BcorΔE9-10/y), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. BcorΔE9-10/y mice developed lethal T-ALL in a similar manner to BcorΔE4/y mice, whereas BcorΔE9-10/y hematopoietic cells showed a growth advantage in the myeloid compartment that was further enhanced by the concurrent deletion of Tet2. Tet2Δ/ΔBcorΔE9-10/y mice developed lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis, and the morphological dysplasia of blood cells. Tet2Δ/ΔBcorΔE9-10/y MDS cells reproduced MDS or evolved into lethal MDS/myeloproliferative neoplasms in secondary recipients. Transcriptional profiling revealed the derepression of myeloid regulator genes of the Cebp family and Hoxa cluster genes in BcorΔE9-10/y progenitor cells and the activation of p53 target genes specifically in MDS erythroblasts where massive apoptosis occurred. Our results reveal a tumor suppressor function of BCOR in myeloid malignancies and highlight the impact of Bcor insufficiency on the initiation and progression of MDS.

Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on GEO dataset

2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao
Keyword(s):  
Heart Failure ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Insulin Signaling Pathway ◽  
Failing Heart

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Methods: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using DAVID website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. Results: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. Conclusions: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

2010 ◽  
Vol 41 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Linda M. Sanderson ◽  
Mark V. Boekschoten ◽  
Beatrice Desvergne ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Target Genes ◽  
Glucose Utilization ◽  
Plasma Cholesterol ◽  
Transcriptional Profiling ◽  
Regulation Of Gene Expression ◽  
Lipoprotein Metabolism ◽  
Peroxisome Proliferator ◽  
Fed State

Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) β/δ in liver. Here we set out to better elucidate the function of PPARβ/δ in liver by comparing the effect of PPARα and PPARβ/δ deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARα and PPARβ/δ deletion was similar, whereas in fasted state the effect of PPARα deletion was much more pronounced, consistent with the pattern of gene expression of PPARα and PPARβ/δ. Minor overlap was found between PPARα- and PPARβ/δ-dependent gene regulation in liver. Pathways upregulated by PPARβ/δ deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARβ/δ deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARβ/δ−/− mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARβ/δ target genes. In contrast to PPARα−/− mice, no changes in plasma free fatty acid, plasma β-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARβ/δ−/− mice. Our data indicate that PPARβ/δ governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver.

scholarly journals Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2318-2326 ◽  
Author(s):  
Jay W. Shin ◽  
Reto Huggenberger ◽  
Michael Detmar
Keyword(s):  
Lymphatic Vessel ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Early Response ◽  
Lymphatic Endothelium ◽  
Induced Genes ◽  
And Migration ◽  
Proliferation And Migration

Abstract Lymphatic vessel growth and activation, mediated by vascular endothelial growth factor (VEGF)–C and/or VEGF-A, have important roles in metastasis and in chronic inflammation. We aimed to comprehensively identify downstream molecular targets induced by VEGF-A or VEGF-C in lymphatic endothelium by analyzing the time-series transcriptional profile of treated human dermal lymphatic endothelial cells (LECs). We identified a number of genes, many not previously known to be involved in lymphangiogenesis, that were characterized either as early response genes, transiently induced genes, or progressively induced genes. Endothelial-specific molecule-1 (ESM-1) was one of the genes that were most potently induced by both VEGF-A and VEGF-C. Whereas ESM-1 induction by VEGF-A was mainly dependent on activation of VEGFR-2, VEGF-C–mediated induction depended on the activity of both VEGFR-2 and VEGFR-3. Incubation of LECs with ESM-1 increased the stimulatory effects of both VEGF-A and VEGF-C on LEC proliferation and migration, whereas ESM-1 alone had no effect. Importantly, VEGF-A (or VEGF-C) induction of LEC proliferation and migration were significantly inhibited by siRNA-mediated silencing of ESM-1 in vitro and in vivo. These studies reveal ESM-1 as a novel mediator of lymphangiogenesis and as a potential target for the inhibition of pathologic lymphatic vessel activation.

scholarly journals The Small Molecule Phenamil Induces Osteoblast Differentiation and Mineralization

2009 ◽  
Vol 29 (14) ◽  
pp. 3905-3914 ◽  
Author(s):  
Kye Won Park ◽  
Hironori Waki ◽  
Woo-Kyun Kim ◽  
Brandon S. J. Davies ◽  
Stephen G. Young ◽  
...  
Keyword(s):  
Small Molecules ◽  
Bone Morphogenetic Proteins ◽  
Osteoblast Differentiation ◽  
Bone Repair ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Osteoblastic Differentiation ◽  
Bmp Signaling ◽  
Matrix Mineralization ◽  
Stimulation Of

ABSTRACT Stimulation of osteoblast differentiation from mesenchymal stem cells is a potential strategy for bone repair. Bone morphogenetic proteins (BMPs) that induce osteoblastic differentiation have been successfully used in humans to treat fractures. Here we outline a new approach to the stimulation of osteoblast differentiation using small molecules that stimulate BMP activity. We have identified the amiloride derivative phenamil as a stimulator of osteoblast differentiation and mineralization. Remarkably, phenamil acts cooperatively with BMPs to induce the expression of BMP target genes, osteogenic markers, and matrix mineralization in both mesenchymal stem cell lines and calvarial organ cultures. Transcriptional profiling of cells treated with phenamil led to the identification of tribbles homolog 3 (Trb3) as a mediator of its effects. Trb3 is induced by phenamil selectively in cells with osteoblastic potential. Both Trb3 and phenamil stabilize the expression of SMAD, the critical transcription factor in BMP signaling, by promoting the degradation of SMAD ubiquitin regulatory factor 1. Small interfering RNA-mediated knockdown of Trb3 blunts the effects of phenamil on BMP signaling and osteogenesis. Thus, phenamil induces osteogenic differentiation, at least in part, through Trb3-dependent promotion of BMP action. The synergistic use of small molecules such as phenamil along with BMPs may provide new strategies for the promotion of bone healing.

scholarly journals Mutation in FBXO32 causes dilated cardiomyopathy through up-regulation of ER-stress mediated apoptosis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nadya Al-Yacoub ◽  
Dilek Colak ◽  
Salma Awad Mahmoud ◽  
Maya Hammonds ◽  
Kunhi Muhammed ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Er Stress ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Underlying Mechanism ◽  
Effector Proteins ◽  
Homozygous Mutation ◽  
Unfolded Protein ◽  
Canonical Pathways ◽  
The Unfolded Protein Response

AbstractEndoplasmic reticulum (ER) stress induction of cell death is implicated in cardiovascular diseases. Sustained activation of ER-stress induces the unfolded protein response (UPR) pathways, which in turn activate three major effector proteins. We previously reported a missense homozygous mutation in FBXO32 (MAFbx, Atrogin-1) causing advanced heart failure by impairing autophagy. In the present study, we performed transcriptional profiling and biochemical assays, which unexpectedly revealed a reduced activation of UPR effectors in patient mutant hearts, while a strong up-regulation of the CHOP transcription factor and of its target genes are observed. Expression of mutant FBXO32 in cells is sufficient to induce CHOP-associated apoptosis, to increase the ATF2 transcription factor and to impair ATF2 ubiquitination. ATF2 protein interacts with FBXO32 in the human heart and its expression is especially high in FBXO32 mutant hearts. These findings provide a new underlying mechanism for FBXO32-mediated cardiomyopathy, implicating abnormal activation of CHOP. These results suggest alternative non-canonical pathways of CHOP activation that could be considered to develop new therapeutic targets for the treatment of FBXO32-associated DCM.

scholarly journals Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure

2019 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao
Keyword(s):  
Heart Failure ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Normal Heart ◽  
Developmental Progress

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure developmental progress also are largely unclear.Methods: The transcriptional profiling of heart failure was identified from integrated gene expression datasets. The enriched pathways and transcription factors were analyzed using DAVID and GSEA assay. The transcriptional networks were created by Cytoscape.Results: Compared with the normal heart tissues, we found 90 genes were particularly differentially expressed in heart failing tissues, and those genes were associated with multiple metabolism pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in heart failing tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of heart failing tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in heart failing tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were decreased in heart failing tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed the transcription factor MYC and C/EBPβ mediated regulatory networks in heart failing tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the failure developmental progress by literature research. Conclusions: Our results suggested that transcription factor MYC and C/EBPβ played critical roles in heart failure developmental progress. And new heart failure treatments may be developed by targeting MYC and C/EBPβ.

scholarly journals Evolution of the complex transcription network controlling biofilm formation in Candida species

2020 ◽  
Author(s):  
Eugenio Mancera ◽  
Isabel Nocedal ◽  
Stephen Hammel ◽  
Megha Gulati ◽  
Kaitlin F. Mitchell ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Microbial Colonization ◽  
Master Regulator ◽  
Transcription Network ◽  
Network Information ◽  
Master Regulators ◽  
Extant Species

ABSTRACTWe examine how a complex transcription network composed of seven “master” regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. The ability to form biofilms is crucial for microbial colonization of different host niches, particularly when an implanted medical device is present. We examined and compared the network underlying biofilm formation across four Candida species (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis), all of which form biofilms composed of multiple cell types. To describe the salient features of the network across different species, we employed four approaches: (1) we phenotypically characterized the biofilms formed by these species using a variety of methods; (2) we knocked out — one by one — the master regulators identified in C. albicans in the four species and monitored their effect on biofilm formation; (3) we identified the target genes of 18 master regulator orthologs across the four species by performing ChIP-seq experiments; and (4) we carried out transcriptional profiling across each species during biofilm formation. Additional network information was obtained by analyzing an interspecies hybrid formed between the two most closely related species, C. albicans and C. dubliniensis. We observed two major types of changes that have occurred in the biofilm circuit since the four species last shared a common ancestor. Master regulator “substitutions” occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. Both types of change are crucial to account for the structures of the biofilm networks in extant species. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.

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