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GSE83716
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Interferon (IFN) is a unique type I IFN that is not induced by pattern-recognition response elements. IFN is constitutively expressed in mucosal tissues including the female genital mucosa. We show here that IFN induces an antiviral state in human macrophages that blocks HIV-1 replication.
Publication Title
IFN-<b>ε</b> protects primary macrophages against HIV infection.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Publication Title
Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study, we evaluated the PK/PD and explored the efficacy of a PDE4 inhibitor, CC-11050 in a murine model of Mtb infection. Infected mouse lungs with or without CC-11050 treatment was also used to interrogate genome-wide transcriptional changes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt ligands signal in many mammalian tissues, including the intestinal epithelium, where constitutive signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted transcription factor CDX2 in colonic cells uncovered highly significant over-representation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling. Chromatin immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy of CDX2 and TCF4 across short distances. A region spanning the single nucleotide polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal cancer risk in humans, represented one of many co-occupied sites. Co-occupancy correlated with intestine-specific gene expression and CDX2 loss reduced TCF4 binding.These results implicate CDX2 in directing TCF4 binding in intestinal cells. Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes.
Publication Title
TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
Cell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Publication Title
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II
Description
We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.
Publication Title
Essential and redundant functions of caudal family proteins in activating adult intestinal genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi
Publication Title
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Sample Metadata Fields
Specimen part
View Samples