Regulatory Network Analyses Reveal Genome-Wide Potentiation of LIF Signaling by Glucocorticoids and Define an Innate Cell Defense Response

Bacterial spot (BS), caused by Xanthomonas campestris pv. Vesicatoria (Xcv), severely affects the quality and yield of pepper. Thus, breeding new pepper cultivars with enhanced resistance to BS can improve economic benefits for pepper production. Identification of BS resistance genes is an essential step to achieve this goal. However, very few BS resistance genes have been well characterized in pepper so far. In this study, we reanalyzed public multiple time points related to RNA-seq data sets from two pepper cultivars, the Xcv-susceptible cultivar ECW and the Xcv-resistant cultivar VI037601, post Xcv infection. We identified a total of 3568 differentially expressed genes (DEGs) between two cultivars post Xcv infection, which were mainly involved in some biological processes, such as Gene Ontology (GO) terms related to defense response to bacterium, immune system process, and regulation of defense response, etc. Through weighted gene co-expression network analysis (WGCNA), we identified 15 hub (Hub) transcription factor (TF) candidates in response to Xcv infection. We further selected 20 TFs from the gene regulatory network (GRN) potentially involved in Xcv resistance response. Finally, we predicted 4 TFs, C3H (p-coumarate 3-hydroxylase), ERF (ethylene-responsive element binding factor), TALE (three-amino-acid-loop-extension), and HSF (heat shock transcription factor), as key factors responsible for BS disease resistance in pepper. In conclusion, our study provides valuable resources for dissecting the underlying molecular mechanism responsible for Xcv resistance in pepper. Additionally, it also provides valuable references for mining transcriptomic data to identify key candidates for disease resistance in horticulture crops.

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Migraine: Genetic Variants and Clinical Phenotypes

Current Medicinal Chemistry ◽

10.2174/0929867325666180719120215 ◽

2019 ◽

Vol 26 (34) ◽

pp. 6207-6221 ◽

Cited By ~ 1

Author(s):

Innocenzo Rainero ◽

Alessandro Vacca ◽

Flora Govone ◽

Annalisa Gai ◽

Lorenzo Pinessi ◽

...

Keyword(s):

Genetic Variants ◽

Association Studies ◽

Mthfr Gene ◽

Genome Wide Association Studies ◽

Clinical Phenotypes ◽

Network Analyses ◽

Genome Wide ◽

Genomic Studies ◽

The Common ◽

The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

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Genome-wide Kinase-Chromatin Interactions Reveal the Regulatory Network of ERK Signaling in Human Embryonic Stem Cells

Molecular Cell ◽

10.1016/j.molcel.2013.04.030 ◽

2013 ◽

Vol 50 (6) ◽

pp. 844-855 ◽

Cited By ~ 61

Author(s):

Jonathan Göke ◽

Yun-Shen Chan ◽

Junli Yan ◽

Martin Vingron ◽

Huck-Hui Ng

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Regulatory Network ◽

Embryonic Stem ◽

Erk Signaling ◽

Chromatin Interactions ◽

Genome Wide

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Abstract MP208: A Shared Fog2 / Tbx5-dependent Gene Regulatory Network Identified By Transcription Factor-dependent Non-coding RNA Profiling Modulates Cardiac Rhythm

Circulation Research ◽

10.1161/res.129.suppl_1.mp208 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Linsin A Smith ◽

Carlos Perez-Cervantes ◽

Michael Broman ◽

Rangarajan Nadadur ◽

Jeff Steimle ◽

...

Keyword(s):

Gene Regulatory Network ◽

Regulatory Network ◽

Cardiac Rhythm ◽

Association Studies ◽

Genome Wide Association ◽

Calcium Handling ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Gene Regulatory ◽

Atrial Rhythm

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting over 33 million individuals throughout the world. AF is highly heritable and recent genome-wide association studies (GWAS) have cumulatively identified over 100 loci associated with AF risk. Genome-wide association studies (GWAS) often identify transcription factor (TF) loci in association with complex human diseases, implying that a significant transcriptional component underlies human disease risk and etiology. The transcription factors ZFPM2 (FOG2), GATA4, and TBX5 have all been implicated in human AF risk by genetic studies. We hypothesized that FOG2, GATA4, and TBX5 functionally interact to regulate a gene regulatory network essential for atrial rhythm control. We generated a novel mouse model of spontaneous AF based on FOG2 overexpression. FOG2 ChIP-seq identified FOG2 genomic localization at loci co-occupied by GATA4, a known FOG2 binding partner. However, we found that FOG2 OE caused gene expression alterations that correlated more highly with TBX5-dependent rather than GATA4-dependent gene expression, including a module of calcium handling genes required for atrial rhythm homeostasis. We applied TF-dependent non-coding transcriptional profiling to examine the FOG2 dependent atrial GRN, which identified 805 candidate regulatory regions with accessible chromatin and FOG2 dependent ncRNAs. TBX5 removal and FOG2 OE caused highly correlated dysregulation of ncRNA expression at open chromatin regions genome-wide, suggesting a functional interaction between TBX5 and FOG2. Furthermore, FOG2 OE only affected enhancer activity by altered ncRNA abundance at locations of TBX5 co-binding. The shared TBX5/FOG2 genomic interaction predicted a potential genetic interaction, and we found that cardiac rhythm abnormalities caused by Tbx5 haploinsufficiency were rescued by Fog2 haploinsufficiency. Taken together, TF-dependent ncRNA-profiling revealed an interconnected cardiac rhythm gene regulatory network (GRN) between FOG2, TBX5 and GATA4. These data nominate a specific model in which FOG2 is recruited by GATA4 to modulate a co-bound TBX5-dependent atrial gene regulatory network for calcium handling and atrial rhythm homeostasis.

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Measles Contributes to Rheumatoid Arthritis: Evidence from Pathway and Network Analyses of Genome-Wide Association Studies

PLoS ONE ◽

10.1371/journal.pone.0075951 ◽

2013 ◽

Vol 8 (10) ◽

pp. e75951 ◽

Cited By ~ 19

Author(s):

Guiyou Liu ◽

Yongshuai Jiang ◽

Xiaoguang Chen ◽

Ruijie Zhang ◽

Guoda Ma ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Network Analyses ◽

Genome Wide

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Identification of miRNAs Involved in Bacillus velezensis FZB42-Activated Induced Systemic Resistance in Maize

International Journal of Molecular Sciences ◽

10.3390/ijms20205057 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5057 ◽

Cited By ~ 1

Author(s):

Shanshan Xie ◽

Hengguo Yu ◽

Enze Li ◽

Yu Wang ◽

Juan Liu ◽

...

Keyword(s):

Defense Response ◽

Target Genes ◽

Induced Systemic Resistance ◽

Systemic Resistance ◽

Abiotic Stress Response ◽

Bacillus Velezensis ◽

Nuclear Factor Y ◽

Network Analyses ◽

Cis Element ◽

Differentially Expressed Mirna

Bacillus velezensis FZB42 is able to activate induced systemic resistance (ISR) to enhance plant defense response against pathogen infections. Though the roles of microRNAs (miRNAs) in Bacillus-triggered ISR have been reported in Arabidopsis, the maize miRNAs responsible for the Bacillus-activated ISR process have not been discovered. To explore the maize miRNAs involved in ISR, maize miRNAs in response to FZB42 (ISR activating), FZB42△sfp△alss (deficient in triggering ISR), and a control for 12 h were sequenced. A total of 146 known miRNAs belonging to 30 miRNA families and 217 novel miRNAs were identified. Four miRNAs specifically repressed in FZB42-treatment were selected as candidate ISR-associated miRNAs. All of them contained at least one defense response-related cis-element, suggesting their potential roles in activating the ISR process. Interestingly, three of the four candidate ISR-associated miRNAs belong to the conserved miR169 family, which has previously been confirmed to play roles in abiotic stress response. Moreover, 52 mRNAs were predicted as potential targets of these candidate ISR-associated miRNAs through TargetFinder software and degradome sequencing. Gene Ontology (GO) and network analyses of target genes showed that these differentially expressed miRNA might participate in the ISR process by regulating nuclear factor Y transcription factor. This study is helpful in better understanding the regulatory roles of maize miRNAs in the Bacillus-activated ISR process.

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Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers

Disease Markers ◽

10.1155/2020/8884450 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Dan Wang ◽

Mingyue Li ◽

Jing Li ◽

Xuechao Wan ◽

Yan Huang ◽

...

Keyword(s):

Signaling Pathway ◽

Cancer Progression ◽

Regulatory Network ◽

Bioinformatics Analysis ◽

Mapk Signaling ◽

Ppi Network ◽

Network Analyses ◽

Comprehensive Characterization ◽

Upstream Regulators

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

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