scholarly journals Genome-Wide Analysis of Glucocorticoid-Responsive Transcripts in the Hypothalamic Paraventricular Region of Male Rats

Endocrinology ◽  
2018 ◽  
Vol 160 (1) ◽  
pp. 38-54 ◽  
Author(s):  
Keiichi Itoi ◽  
Ikuko Motoike ◽  
Ying Liu ◽  
Sam Clokie ◽  
Yasumasa Iwasaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Receptor Gene ◽  
Male Rats ◽  
Regulatory Mechanisms ◽  
High Dose ◽  
Sequencing Analysis ◽  
Reverse Transcription Pcr ◽  
Genome Wide ◽  
A Genome

Abstract Glucocorticoids (GCs) are essential for stress adaptation, acting centrally and in the periphery. Corticotropin-releasing factor (CRF), a major regulator of adrenal GC synthesis, is produced in the paraventricular nucleus of the hypothalamus (PVH), which contains multiple neuroendocrine and preautonomic neurons. GCs may be involved in diverse regulatory mechanisms in the PVH, but the target genes of GCs are largely unexplored except for the CRF gene (Crh), a well-known target for GC negative feedback. Using a genome-wide RNA-sequencing analysis, we identified transcripts that changed in response to either high-dose corticosterone (Cort) exposure for 12 days (12-day high Cort), corticoid deprivation for 7 days (7-day ADX), or acute Cort administration. Among others, canonical GC target genes were upregulated prominently by 12-day high Cort. Crh was upregulated or downregulated most prominently by either 7-day ADX or 12-day high Cort, emphasizing the recognized feedback effects of GC on the hypothalamic-pituitary-adrenal (HPA) axis. Concomitant changes in vasopressin and apelin receptor gene expression are likely to contribute to HPA repression. In keeping with the pleotropic cellular actions of GCs, 7-day ADX downregulated numerous genes of a broad functional spectrum. The transcriptome response signature differed markedly between acute Cort injection and 12-day high Cort. Remarkably, six immediate early genes were upregulated 1 hour after Cort injection, which was confirmed by quantitative reverse transcription PCR and semiquantitative in situ hybridization. This study may provide a useful database for studying the regulatory mechanisms of GC-dependent gene expression and repression in the PVH.

Genetic Polymorphisms in the Promoter Region of the beta-2 Adrenergic Receptor Are Associated with the Early Response of Acute Lymphoblastic Leukemia to Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1959-1959
Author(s):  
Meyling H. Cheok ◽  
Cong Ding ◽  
Wenjian Yang ◽  
Somas Das ◽  
Dario Campana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Adrenergic Receptor ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
High Dose ◽  
A Genome ◽  
Adrb2 Gene ◽  
Beta 2

Abstract Acute lymphoblastic leukemia (ALL) in children is a paradigm of disseminated cancer that is curable with chemotherapy, yet current treatment fails to cure about 20% of patients, for reasons that remain unknown. In a genome-wide assessment of in vivo treatment-induced changes in gene expression in ALL cells using the Affymetrix U95A and U133A oligonucleotide microarray, we found that patients who eventually relapsed did not up-regulate expression of the pro-apoptotic beta-2 adrenergic receptor gene (ADRB2) in their ALL cells after initial treatment with methotrexate and mercaptopurine. After treatment we observed a 5-fold lower level of ADRB2 gene expression in leukemia cells of patients who ultimately relapsed. We found a common genetic polymorphism in the ADRB2 promoter that was significantly linked to high-dose methotrexate induced up-regulation in ADRB2 gene expression in ALL cells. Moreover, the ADRB2 promoter haplotype was significantly linked to poor early treatment response in ALL cells from 242 children (i.e., probability of event-free survival at two years, p=0.0275 stratified by risk groups). These findings have revealed a germline polymorphism that is linked to the early antileukemic effects of ALL chemotherapy and provide new insights into genetic determinants of ALL treatment efficacy.

scholarly journals Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

2021 ◽  
Vol 17 ◽  
pp. 117693432110413
Author(s):  
Chaoxin Zhang ◽  
Tao Wang ◽  
Tongyan Cui ◽  
Shengwei Liu ◽  
Bing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Genome Wide ◽  
A Genome

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPβ, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

scholarly journals DNA methylation during human adipogenesis and the impact of fructose

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Giulia Tini ◽  
Vijayalakshmi Varma ◽  
Rosario Lombardo ◽  
Greg T. Nolen ◽  
Gregory Lefebvre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Time Dependent ◽  
Regulatory Mechanisms ◽  
Differentially Methylated Regions ◽  
Genome Wide ◽  
A Genome ◽  
Final Maturation ◽  
The Impact

Abstract Background Increased adipogenesis and altered adipocyte function contribute to the development of obesity and associated comorbidities. Fructose modified adipocyte metabolism compared to glucose, but the regulatory mechanisms and consequences for obesity are unknown. Genome-wide methylation and global transcriptomics in SGBS pre-adipocytes exposed to 0, 2.5, 5, and 10 mM fructose, added to a 5-mM glucose-containing medium, were analyzed at 0, 24, 48, 96, 192, and 384 h following the induction of adipogenesis. Results Time-dependent changes in DNA methylation compared to baseline (0 h) occurred during the final maturation of adipocytes, between 192 and 384 h. Larger percentages (0.1% at 192 h, 3.2% at 384 h) of differentially methylated regions (DMRs) were found in adipocytes differentiated in the glucose-containing control media compared to adipocytes differentiated in fructose-supplemented media (0.0006% for 10 mM, 0.001% for 5 mM, and 0.005% for 2.5 mM at 384 h). A total of 1437 DMRs were identified in 5237 differentially expressed genes at 384 h post-induction in glucose-containing (5 mM) control media. The majority of them inversely correlated with the gene expression, but 666 regions were positively correlated to the gene expression. Conclusions Our studies demonstrate that DNA methylation regulates or marks the transformation of morphologically differentiating adipocytes (seen at 192 h), to the more mature and metabolically robust adipocytes (as seen at 384 h) in a genome-wide manner. Lower (2.5 mM) concentrations of fructose have the most robust effects on methylation compared to higher concentrations (5 and 10 mM), suggesting that fructose may be playing a signaling/regulatory role at lower concentrations of fructose and as a substrate at higher concentrations.

scholarly journals Identifying functional targets from transcription factor binding data using SNP perturbation

2018 ◽  
Author(s):  
Jing Xiang ◽  
Seyoung Kim
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Graphical Models ◽  
Target Genes ◽  
Expression Data ◽  
Genome Wide ◽  
Binding Data ◽  
A Genome ◽  
Trait Locus ◽  
Locus Mapping

AbstractTranscription factors (TFs) play a key role in transcriptional regulation by binding to DNA to initiate the transcription of target genes. Techniques such as ChIP-seq and DNase-seq provide a genome-wide map of TF binding sites but do not offer direct evidence that those bindings affect gene expression. Thus, these assays are often followed by TF perturbation experiments to determine functional binding that leads to changes in target gene expression. However, such perturbation experiments are costly and time-consuming, and have a well-known limitation that they cannot distinguish between direct and indirect targets. In this study, we propose to use the naturally occurring perturbation of gene expression by genetic variation captured in population SNP and expression data to determine functional targets from TF binding data. We introduce a computational methodology based on probabilistic graphical models for isolating the perturbation effect of each individual SNP, given a large number of SNPs across genomes perturbing the expression of all genes simultaneously. Our computational approach constructs a gene regulatory network over TFs, their functional targets, and further downstream genes, while at the same time identifying the SNPs perturbing this network. Compared to experimental perturbation, our approach has advantages of identifying direct and indirect targets, and leveraging existing data collected for expression quantitative trait locus mapping, a popular approach for studying the genetic architecture of expression. We apply our approach to determine functional targets from the TF binding data for a lymphoblastoid cell line from the ENCODE Project, using SNP and expression data from the HapMap 3 and 1000 Genomes Project samples. Our results show that from TF binding data, functional target genes can be determined by SNP perturbation of various aspects that impact transcriptional regulation, such as TF concentration and TF-DNA binding affinity.

scholarly journals Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3724-3733 ◽  
Author(s):  
Louis C. Doré ◽  
Timothy M. Chlon ◽  
Christopher D. Brown ◽  
Kevin P. White ◽  
John D. Crispino
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Gata Factor ◽  
Related Factors ◽  
Genome Wide ◽  
A Genome

Abstract There are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than one-third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression; and in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we show that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification.

scholarly journals Genome-Wide Characterization of the SloR Metalloregulome in Streptococcus mutans

2009 ◽  
Vol 192 (5) ◽  
pp. 1433-1443 ◽  
Author(s):  
Kevin P. O'Rourke ◽  
Jeremy D. Shaw ◽  
Mitchell W. Pesesky ◽  
Brian T. Cook ◽  
Susanne M. Roberts ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Metal Ion ◽  
Target Genes ◽  
Treatment Strategies ◽  
Virulence Gene ◽  
Reverse Transcription Pcr ◽  
Genome Wide ◽  
A Genome ◽  
Recognition Elements

ABSTRACT Streptococcus mutans is the primary causative agent of human dental caries, a ubiquitous infectious disease for which effective treatment strategies remain elusive. We investigated a 25-kDa SloR metalloregulatory protein in this oral pathogen, along with its target genes that contribute to cariogenesis. Previous studies have demonstrated manganese- and SloR-dependent repression of the sloABCR metal ion transport operon in S. mutans. In the present study, we demonstrate that S. mutans coordinates this repression with that of certain virulence attributes. Specifically, we noted virulence gene repression in a manganese-containing medium when SloR binds to promoter-proximal sequence palindromes on the S. mutans chromosome. We applied a genome-wide approach to elucidate the sequences to which SloR binds and to reveal additional “class I” genes that are subject to SloR- and manganese-dependent repression. These analyses identified 204 S. mutans genes that are preceded by one or more conserved palindromic SloR recognition elements (SREs). We cross-referenced these genes with those that we had identified previously as SloR and/or manganese modulated in microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) experiments. From this analysis, we identified a number of S. mutans virulence genes that are subject to transcriptional upregulation by SloR and noted that such “class II”-type regulation is dependent on direct SloR binding to promoter-distal SREs. These observations are consistent with a bifunctional role for the SloR metalloregulator and implicate it as a target for the development of therapies aimed at alleviating S. mutans-induced caries formation.

scholarly journals The mutL Gene as a Genome-Wide Taxonomic Marker for High Resolution Discrimination of Lactiplantibacillus plantarum and Its Closely Related Taxa

2021 ◽  
Vol 9 (8) ◽  
pp. 1570
Author(s):  
Chien-Hsun Huang ◽  
Chih-Chieh Chen ◽  
Yu-Chun Lin ◽  
Chia-Hsuan Chen ◽  
Ai-Yun Lee ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Target Genes ◽  
Marker Genes ◽  
Rrna Gene ◽  
Accurate Identification ◽  
Discrimination Power ◽  
Sequence Identity ◽  
Genome Wide ◽  
A Genome

The current taxonomy of the Lactiplantibacillus plantarum group comprises of 17 closely related species that are indistinguishable from each other by using commonly used 16S rRNA gene sequencing. In this study, a whole-genome-based analysis was carried out for exploring the highly distinguished target genes whose interspecific sequence identity is significantly less than those of 16S rRNA or conventional housekeeping genes. In silico analyses of 774 core genes by the cano-wgMLST_BacCompare analytics platform indicated that csbB, morA, murI, mutL, ntpJ, rutB, trmK, ydaF, and yhhX genes were the most promising candidates. Subsequently, the mutL gene was selected, and the discrimination power was further evaluated using Sanger sequencing. Among the type strains, mutL exhibited a clearly superior sequence identity (61.6–85.6%; average: 66.6%) to the 16S rRNA gene (96.7–100%; average: 98.4%) and the conventional phylogenetic marker genes (e.g., dnaJ, dnaK, pheS, recA, and rpoA), respectively, which could be used to separat tested strains into various species clusters. Consequently, species-specific primers were developed for fast and accurate identification of L. pentosus, L. argentoratensis, L. plantarum, and L. paraplantarum. During this study, one strain (BCRC 06B0048, L. pentosus) exhibited not only relatively low mutL sequence identities (97.0%) but also a low digital DNA–DNA hybridization value (78.1%) with the type strain DSM 20314T, signifying that it exhibits potential for reclassification as a novel subspecies. Our data demonstrate that mutL can be a genome-wide target for identifying and classifying the L. plantarum group species and for differentiating novel taxa from known species.

scholarly journals Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Mehta ◽  
Karen Grewen ◽  
Brenda Pearson ◽  
Shivangi Wani ◽  
Leanne Wallace ◽  
...  
Keyword(s):  
Gene Expression ◽  
Depressive Symptoms ◽  
Postpartum Depression ◽  
Expression Profiles ◽  
Depression Scale ◽  
Well Being ◽  
Health Concern ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Gene Expression

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

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