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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [whole lung]

ABSTRACT: The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

ORGANISM(S): Mus musculus

PROVIDER: GSE83612 | GEO | 2016/09/09

SECONDARY ACCESSION(S): PRJNA326508

REPOSITORIES: GEO

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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [neutrophils]

Project description:The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

2016-09-09 | GSE83613 | GEO

Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

Project description:Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

| PRJNA326501 | ENA

Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

Project description:Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

2021-03-31 | GSE150760 | GEO

Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggesssive Murine Hepatoblastomas

Project description:The pediatric liver cancer hepatoblastoma (HB) often expresses mutant forms of b-catenin and dysregulates the Hippo tumor suppressor pathway. Murine HBs can be generated by co-expressing b-catenin mutants and the constitutively active Hippo effector YAPS127A. Some human HBs also express mutant forms of NFE2L2/NRF2 (NFE2L2), a bHLH transcription factor that tempers oxidative and electrophilic stress. In doing so, NFE2L2 either suppresses or facilitates tumorigenesis in a context- and time-dependent manner. We show here that two patient-derived NFE2L2 missense mutants, L30P and R34P, markedly accelerate HB growth in association with diffuse cyst formation, an otherwise uncommon feature of human HB. Surprisingly, we found that any two members of the mutant b-catenin-YAPS127A-L30P/R34P triad were tumorigenic, thus providing direct evidence for NFE2L2’s oncogenicity. Each tumor group showed distinct features but shared a similarly deregulated set of 22 transcripts, 10 of which perfectly correlated with survival in human HBs. 17 transcripts also correlated with survival in multiple cancers. One of the most deregulated transcripts encoded Serpin E1, a serine protease inhibitor with roles in fibrinolysis, tumor growth and extracellular matrix formation. The combination of mutant b-catenin-YAPS127A-Serpin E1 neither accelerated tumor growth nor generated cysts but did promote large-scale necrosis that was often associated with the cysts seen in mutant b-catenin-YAPS127A-L30P/R34P tumor, albeit on a lesser scale. These findings establish the direct oncogencity of NFE2L2 mutants and identify key transcripts, including Serpin E1, that impact tumor growth and other HB features.

2021-05-20 | GSE157623 | GEO

Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

Project description:Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

| PRJNA633526 | ENA

Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggesssive Murine Hepatoblastomas

Project description:Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggesssive Murine Hepatoblastomas

| PRJNA662245 | ENA

Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-09-09 | GSE83615 | GEO

Comparison of the transcriptomic impact of NRF2 depletion with that of NUAK1 depletion in SW480 colorectal cancer cells

Project description:The intent of the experiment is to determine how much of NRF2 (NFE2L2)-dependent transcription requires NUAK1 upstream. SW480 cells were transfected with siRNA targeting either NRF2, NUAK1 or non-targeting control, and harvested for analysis by RNA-SEQ 48hrs after transfection. mRNA was analysed by Illumina paired-end RNA-SEQ

2018-02-19 | E-MTAB-6264 | biostudies-arrayexpress

Identification of Novel NRF2-Regulated Genes by ChIPSeq

Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high-confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRAhas implications for response to retinoid treatments and adipogenesis. In mouse 3T3-L1 cells SFN treatment affected Rxra expression early in adipogenesis and knockdown of Nrf2 delayed Rxra expression, both leading to impaired adipogenesis. ChIP-Seq analysis of NRF2 binding sites in human lymphoblastoid cells treated with sulforaphane or vehicle

2012-06-18 | E-GEOD-37589 | biostudies-arrayexpress

Reduced expression of RBM47 enhances Nrf2 activity to promote tumor growth in A549 lung adenocarcinoma cells

Project description:We identified RNA binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-beta in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition (EMT). TGF-beta repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast, and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-beta. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor suppressive roles for RBM47 through the inhibition of Nrf2 activity. Effect of shRNA for RBM47 and TGF-beta on gene expression was evaluated by RNA-seq and RBM47-bound RNAs were identified by RIP-seq in A549 cells.

2016-03-01 | E-GEOD-61910 | biostudies-arrayexpress

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