S93 Correlation of eotaxin-3 gene expression and other IL-13-induced genes in patients with asthma

ABSTRACT Acinetobacter species encounter cycles of feast and famine in nature. We show that populations of A cinetobacter baylyi strain ADP1 remain dynamic for 6 weeks in batch culture. We created a library of lacZ reporters inserted into SalI sites in the genome and then isolated 30 genes with lacZ insertions whose expression was induced by starvation during long-term stationary phase compared with their expression during exponential growth. The genes encode metabolic, gene expression, DNA maintenance, envelope, and conserved hypothetical proteins.

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Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and Apc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis

BioMed Research International ◽

10.1155/2016/1310342 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Angelo Pietro Femia ◽

Cristina Luceri ◽

Maura Lodovici ◽

Stefania Crucitta ◽

Giovanna Caderni

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Expression Profile ◽

Antioxidant Status ◽

Genotoxic Stress ◽

Rt Pcr ◽

Induced Genes ◽

Stress Related Genes ◽

Microarray Technique ◽

Unsupervised Cluster Analysis

Apc-mutated Pirc rats, spontaneously developing intestinal tumours, are resistant to 1,2-dimethylhydrazine- (DMH-) induced colon apoptosis. To understand this phenomenon, we analyzed the expression of genotoxic stress-related genes Mgmt, Gsta1, and Gstp1 in the colon of wt and Pirc rats in basal conditions and 24 h after DMH; plasmatic oxidant/antioxidant status was also evaluated. After DMH, Mgmt expression was increased in both genotypes but significantly only in wt rats; Gsta1 expression was significantly increased in both genotypes. Gstp1 expression did not vary after DMH but was lower in Pirc rats. Moreover, for each genotype, we studied by microarray technique whole gene expression profile after DMH. By unsupervised cluster analysis, 28 genes were differentially modulated between the two genotypes. Among them were interferon-induced genes Irf7, Oas1a, Oasl2, and Isg15 and the transcription factor Taf6l, overexpressed in DMH-treated wt rats and unchanged in Pirc rats. RT-PCR confirmed their overexpression in DMH-treated wt rats and showed a slighter variation in DMH-treated Pirc rats. Taken together, despite a blunted induction of Irf7, Oas1a, and Mgmt, defective apoptosis in Pirc rats 24 h after DMH is not mirrored by major differences in gene expression compared with wt rats.

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PP2B-mediated Dephosphorylation of c-Jun C Terminus Regulates Phorbol Ester-induced c-Jun/Sp1 Interaction in A431 Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e06-09-0797 ◽

2007 ◽

Vol 18 (3) ◽

pp. 1118-1127 ◽

Cited By ~ 13

Author(s):

Ben-Kuen Chen ◽

Chi-Chen Huang ◽

Wei-Chiao Chang ◽

Yun-Ju Chen ◽

Ushio Kikkawa ◽

...

Keyword(s):

Gene Expression ◽

Small Interfering Rna ◽

Neuronal Nicotinic Acetylcholine Receptor ◽

A431 Cells ◽

Keratin 16 ◽

Cytosolic Phospholipase ◽

C Terminus ◽

Genes Expression ◽

Induced Genes ◽

Interfering Rna

The c-Jun/Sp1 interaction is essential for growth factor- and phorbol 12-myristate 13-acetate (PMA)-induced genes expression, including human 12(S)-lipoxygenase, keratin 16, cytosolic phospholipase A2, p21WAF1/CIP1, and neuronal nicotinic acetylcholine receptor β4. Here, we examined the mechanism underlying the PMA-induced regulation on the interaction between c-Jun and Sp1. We found that treatment of cells with PMA induced a dephosphorylation at the C terminus of c-Jun at Ser-243 and a concomitant inhibition of PP2B by using PP2B small interfering RNA, resulting in reduction of PMA-induced gene expression as well as the c-Jun/Sp1 interaction. The c-Jun mutant TAM-67-3A, which contains three substitute alanines at Thr-231, Ser-243, and Ser-249 compared with TAM-67, binds more efficaciously with Sp1 and is about twice as efficacious as TAM-67 in inhibiting the PMA-induced activation of the 12(S)-lipoxygenase promoter. Importantly, PP2B not only dephosphorylates the c-Jun at Ser-243 but also interacts with c-Jun in PMA-treated cells. PMA stimulates the association of the PP2B/c-Jun/Sp1 complex with the promoter. These findings indicate the dephosphorylation of c-Jun C terminus is required for the c-Jun/Sp1 interaction and reveal that PP2B plays an important role in regulating c-Jun/Sp1 interaction in PMA-induced gene expression.

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IL-10 induces gene expression in macrophages: partial overlap with IL-5 but not with IL-4 induced genes

Cytokine ◽

10.1016/s1043-4666(03)00270-9 ◽

2003 ◽

Vol 24 (1-2) ◽

pp. 46-56 ◽

Cited By ~ 12

Author(s):

Rita Stumpo ◽

Manfred Kauer ◽

Stephan Martin ◽

Hubert Kolb

Keyword(s):

Gene Expression ◽

Induced Genes ◽

Partial Overlap

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IL-12 selectively programs effector pathways that are stably expressed in human CD8+ effector memory T cells in vivo

Blood ◽

10.1182/blood-2011-05-357111 ◽

2011 ◽

Vol 118 (14) ◽

pp. 3890-3900 ◽

Cited By ~ 32

Author(s):

Fatema Z. Chowdhury ◽

Hilario J. Ramos ◽

Laurie S. Davis ◽

James Forman ◽

J. David Farrar

Keyword(s):

Gene Expression ◽

Central Memory ◽

Effector Memory ◽

Stable Gene ◽

Memory Cells ◽

Effector Functions ◽

Central Memory Cells ◽

Induced Genes ◽

Unique Program

Abstract CD8+ cytotoxic T lymphocytes play a major role in defense against intracellular pathogens, and their functions are specified by antigen recognition and innate cytokines. IL-12 and IFN-α/β are potent “signal 3” cytokines that are involved in both effector and memory cell development. Although the majority of effector cells are eliminated as inflammation resolves, some survive within the pool of memory cells and retain immediate effector function. In this study, we demonstrate that IL-12 instructs a unique program of effector cell differentiation that is distinct from IFN-α/β. Moreover, effector memory (TEM) cells within peripheral blood display many common attributes of cells differentiated in vitro in response to IL-12, including proinflammatory cytokine secretion and lytic activity. A pattern of IL-12–induced genes was identified that demarcate TEM from central memory cells, and the ontologies of these genes correlated precisely with their effector functions. Further, we uncovered a unique program of gene expression that was acutely regulated by IL-12 and reflected in stable gene expression patterns within TEM, but not T central memory cells in vivo. Thus, this study directly links a selective set of IL-12–induced genes to the programming of effector functions within the stable population of human CD8+ TEM cells in vivo.

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A Short Pulse of Prostaglandin E2 (PGE2) Induces Long Term Chromatin Changes in Hematopoietic Stem Cells Leading to Increased Self-Renewal and Engraftment

Blood ◽

10.1182/blood.v126.23.246.246 ◽

2015 ◽

Vol 126 (23) ◽

pp. 246-246

Author(s):

Eva M Fast ◽

Ellen M Durand ◽

Audrey Sporrij ◽

Leslie Ojeaburu ◽

Rebecca Maher ◽

...

Keyword(s):

Gene Expression ◽

Open Chromatin ◽

Advisory Committees ◽

Self Renewal ◽

Hematopoietic Stem ◽

Human Cd34 ◽

Cd34 Cells ◽

Equity Ownership ◽

Induced Genes

Abstract Hematopoietic stem cells (HSCs) offer promising treatment options for many blood diseases. We have previously identified Prostaglandin E2 (PGE2), a small molecule that increased HSC numbers in the zebrafish embryo. In an adult mammalian transplantation setting a two hour treatment significantly enhanced HSC engraftment. Currently PGE2 is being tested in a phase 2 clinical trial to improve cord blood transplants. To better understand PGE2 effect on HSCs mouse multipotent progenitors (MPP), short term (ST) HSCs, and long term (LT) HSCs were isolated via FACS and given a two hour pulse of PGE2 followed by a competitive transplantation assay. Surprisingly, PGE2 treatment mainly affected ST-HSCs by dramatically prolonging their ability to contribute to peripheral blood. The effect of the two hour treatment persisted through secondary competitive transplants in which robust peripheral blood chimerism of ST-HSCs was evident even 1.5 years after having been exposed to the drug. To elucidate underlying molecular changes gene expression right after PGE2 treatment as well as in ST-HSCs after transplantation was assessed. PGE2 target genes were divided into two categories; "transiently induced" and "permanently induced" genes. Most of the transcripts upregulated two hour after PGE2 treatment were "transiently induced" meaning that they did not continue to be differentially expressed after transplantation. In contrast, a few transcripts including chemokines such as Cxcl2, Cxcl3, members of the Fos gene family as well as Nr4a1, 2 and 3 were both upregulated right after PGE2 treatment as well as in ST-HSCs after transplantation. We classified these genes as "permanently induced". ATAC (Assay for Transposase-Accessible Chromatin)-seq analysis of the transplanted PGE2 treated cells indicated that these "permanently induced" genes maintained a distinctly open chromatin profile in both promotor and enhancer regions, whereas the "transiently induced" genes did not. Gene expression in human CD34+ cells included a signature implying CREB as the main transcription factor responsible for the acute PGE2 response. Phospho-FACS in mouse ST-HSCs and Western-blot analysis in human CD34+ cells confirmed a significant increase in CREB phosphorylation after PGE2 stimulation. Chromatin immunoprecipitation (ChIP)-seq analysis of pCREB was able to identify specific genomic regions where pCREB is recruited to after PGE2 treatment. Compared to unstimulated CD34+ cells an increased binding of pCREB could be detected in promotor regions near transcription start sites. In addition over 90% of de-novo pCREB binding occurred in intergenic and intronic regions. To determine the activation state of these putative enhancers changes in the histone mark H3K27ac and open chromatin state (via ATAC-seq) were assessed after PGE2 treatment. The data suggest that PGE2-induced pCREB binding correlates with remodeling of chromatin already after two hours of drug treatment. Furthermore chromatin sites opened by PGE2 were significantly enriched for the CREB motif both in human CD34+ cells acutely after treatment as well as in mouse ST-HSCs 1.5 years after transplant. In summary this work shows that a two hour treatment with PGE2 is sufficient to confer long-term engraftment properties to ST-HSCs. PGE triggers a chromatin remodeling event through CREB that can permanently alter epigenetic state and gene expression of ST-HSCs. Understanding the self-renewal network induced by PGE2 will not only enrich current clinical applications targeted at increasing engraftable HSC numbers but also further basic understanding of HSC self-renewal. Disclosures Zon: FATE Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder; Scholar Rock: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder.

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A Nonessential HP1-Like Protein Affects Starvation-Induced Assembly of Condensed Chromatin and Gene Expression in Macronuclei of Tetrahymena thermophila

Molecular and Cellular Biology ◽

10.1128/mcb.19.5.3624 ◽

1999 ◽

Vol 19 (5) ◽

pp. 3624-3634 ◽

Cited By ~ 16

Author(s):

Hui Huang ◽

James F. Smothers ◽

Emily A. Wiley ◽

C. David Allis

Keyword(s):

Gene Expression ◽

Tetrahymena Thermophila ◽

Morphological Changes ◽

Condensed Chromatin ◽

Induced Response ◽

Wild Type ◽

Eukaryotic Genes ◽

Associated Proteins ◽

Induced Genes ◽

Dense Chromatin

ABSTRACT Heterochromatin represents a specialized chromatin environment vital to both the repression and expression of certain eukaryotic genes. One of the best-studied heterochromatin-associated proteins isDrosophila HP1. In this report, we have disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1-like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C. D. Allis, Proc. Natl. Acad. Sci. USA 95:13624–13629, 1998). Unlike the Drosophila HP1 gene,HHP1 is not essential in Tetrahymena spp., and during vegetative growth no clear phenotype is observed in cells lacking Hhp1p (ΔHHP1). However, during a shift to nongrowth conditions, the survival rate of ΔHHP1 cells is reduced compared to that of wild-type cells. Upon starvation, Hhp1p becomes hyperphosphorylated concomitant with a reduction in macronuclear volume and an increase in the size of electron-dense chromatin bodies; neither of these morphological changes occurs in the absence of Hhp1p. Activation of two starvation-induced genes (ngoA and CyP) is significantly reduced in ΔHHP1 cells while, in contrast, the expression of several growth-related or constitutively expressed genes is comparable to that in wild-type cells. These results suggest that Hhp1p functions in the establishment and/or maintenance of a specialized condensed chromatin environment that facilitates the expression of certain genes linked to a starvation-induced response.

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Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208659 ◽

2016 ◽

Vol 75 (11) ◽

pp. 2029-2036 ◽

Cited By ~ 70

Author(s):

Juliana Imgenberg-Kreuz ◽

Johanna K Sandling ◽

Jonas Carlsson Almlöf ◽

Jessica Nordlund ◽

Linnea Signér ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Salivary Gland ◽

B Cells ◽

Whole Blood ◽

Minor Salivary Gland ◽

Genome Wide ◽

Induced Genes ◽

Regulatory Effects

ObjectivesIncreasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.MethodsGenome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.ResultsWe identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.ConclusionsOur study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.

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ID: 135: SINGLE CELL GENE EXPRESSION STUDIES IN LUPUS MONOCYTES REVEAL A UNIQUE ANTII-INFLAMMATORY NON-CLASSICAL MONOCYTE POPULATION ASSOCIATED WITH CLINICAL QUIESCENCE

Journal of Investigative Medicine ◽

10.1136/jim-2016-000120.138 ◽

2016 ◽

Vol 64 (4) ◽

pp. 977.2-977

Author(s):

Z Jin ◽

MA Jensen ◽

JM Dorschner ◽

DM Vsetecka ◽

S Amin ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Cell Capture ◽

Gene Set ◽

Inflammatory Gene ◽

Gene Sets ◽

Cell Gene Expression ◽

Induced Genes ◽

Cell Gene ◽

Classical Monocytes

BackgroundOur previous studies have shown that different cell types from the same blood sample demonstrate diverse gene expression parameters. In follow up work, it seems that this diversity extends to cells of the same type from the same blood sample. In this study, we examine single cell gene expression in SLE patient monocytes and determine correlations with clinical features.MethodsCD14++CD16− classical monocytes (CLs) and CD14dimCD16+ non-classical monocytes (NCLs) from SLE patients were purified by magnetic separation. The Fluidigm single cell capture and pre-amplification system was used for single cell capture and target gene pre-amplification. Fluidigm Biomark system (Rt-PCR system) was used to quantify expression of 87 monocyte-related genes. IFN-induced genes in monocytes were identified by culturing monocytes isolated from whole blood of healthy controls with or without IFN-α. Genes significant up-regulated by IFN were identified as IFN-induced genes in current study. An individual cell IFN score was given based upon the sum of expression of IFN-induced genes.ResultsBoth CLs and NCLs demonstrated a wide range of expression of IFN-induced genes, and NCL monocytes had higher IFN scores than CL monocytes. Using unsupervised hierarchical clustering, we found four gene sets that clustered monocytes functionally. These included an IFN-induced gene set, two inflammatory gene sets, and one immunosuppressive gene set. Interestingly, we could define a large subset of NCL monocytes with upregulation of suppressive transcripts (including TGF-β and PDL1) and IFN-induced transcripts were also upregulated, while the two inflammatory gene sets were down-regulated. These cells were highly over-represented in a patient with inactive disease who was on immunosuppressants at the time of blood draw. The proportion of anti-inflammatory gene set expressing NCLs was inversely correlated with anti-dsDNA titers (rho=−0.77, p=0.0051) and positively correlated with C3 complement (rho=0.68, p=0.030) in the SLE patient group, suggesting that these cells are also associated with serological quiescence.ConclusionUsing single cell gene expression, we have identified a unique population of NCL monocytes in SLE patients with upregulation of a combination of anti-inflammatory and IFN-induced transcripts. These cells correspond with clinical and serological quiescence.

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Meta-analysis of immune induced gene expression changes in diverse Drosophila melanogaster innate immune responses

10.1101/2021.09.23.461556 ◽

2021 ◽

Author(s):

Ashley L Waring ◽

Joshua Hill ◽

Brooke M Allen ◽

Nicholas M Bretz ◽

Nguyen Le ◽

...

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Immune Responses ◽

Meta Analysis ◽

Nuclear Factor Κb ◽

Innate Immune ◽

Innate Immune Responses ◽

Response Factors ◽

Induced Genes ◽

Conserved Gene

Background: Organisms are commonly infected by a diverse array of pathogen types including bacteria, fungi, viruses, and parasites, and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression in response to infection. However, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. Results: We performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Conclusions: Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction. These findings provide new insight into transcriptional changes that accompany Drosophila immunity. They may suggest possible roles for the differentially regulated genes in innate immune responses to diverse classes of pathogens, and serve to identify candidate genes for further empirical study of these processes.

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