The cAMP responsive element modulator (CREM) transcription factor influences susceptibility to undernutrition and infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1157406 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30557382_1.fastq.gz | Fastqsanger.gz | |||
| SRR30557382_2.fastq.gz | Fastqsanger.gz | |||
| SRR30557383_1.fastq.gz | Fastqsanger.gz | |||
| SRR30557383_2.fastq.gz | Fastqsanger.gz | |||
| SRR30557384_1.fastq.gz | Fastqsanger.gz |
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Project description:We have identified statistically significant SNPs influencing susceptibility to diarrhea due to Entamoeba histolytica infection at the locus encoding the transcription factor CREM (10p11.21; rs58000832, P=6.1x10-9; rs2148483, P=9.6x10-8) using genome wide association studies (GWAS). Considering undernutrition increases susceptibility to enteric infection, we investigated if CREM locus variants were also associated with nutritional status. Genetic analysis on birth cohorts of Bangladeshi children demonstrated that risk alleles of rs58000832 and rs2148483 were associated with lower weight-for-age z-scores at 12 months of age (rs2148483: 0.188 reduction in WAZ, P= 0.014; rs58000832: 0.135 reduction in WAZ, P= 0.001), independent of E. histolytica diarrhea. Small intestinal transcriptome data from children homozygous for the rs2148483 risk allele compared to heterozygotes demonstrated enrichment of mitochondrial function and catabolism among upregulated genes and enrichment of B-cell activation and adaptive immune pathways among downregulated genes, consistent with dual roles of the CREM locus in immunity and metabolism. Full body deletion and/or intestinal epithelial cell (IEC)-specific deletion of CREM in mice produced decreased body weight. Transcriptome analysis of cecal tissue from E. histolytica challenged mice also showed upregulation of metabolic processes in both full body and IEC-specific deletion mice. Processes with downregulated genes in full body deletion mice were enriched for myeloid cell activation and chemotaxis while immune process changes were absent when deletion was limited to IECs. These data suggest that CREM modulates both metabolism and immune function at mucosal sites.
2025-05-01 | GSE276451 | GEO
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In testis, it is involved in the regulation of spermatogenesis. In this dataset, we include the expression data obtained from wild-type and Crem knock-out mouse testis. 2 condition experiment: 2 strains (WT, Crem-/-). 5 biological replications per condition.
2012-04-10 | E-GEOD-29593 | biostudies-arrayexpress
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In adrenal glands it is involved in the regulation of expression of genes for steroid hormone synthesis. In this dataset, we include the expression data obtained from wild-type and Crem knock-out mouse adrenal glands. 2 condition experiment: 2 strains (WT, Crem-/-). 5 biological replications per condition.
2014-05-25 | E-GEOD-29592 | biostudies-arrayexpress
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In this dataset, we include the expression data obtained from wild-type (WT) and Crem knock-out (KO) mouse liver. Several comparisons were made. KO<WT at 0h, KO<WT at 12 h, 0h<12h in WT and 0h<12h in KO. 4 condition experiment: 2 strains (WT, Crem-/-), 2 time points (0h and 12h). 5 biological replications per condition.
2014-05-25 | E-GEOD-29594 | biostudies-arrayexpress
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In testis, it is involved in the regulation of spermatogenesis. In this dataset, we include the expression data obtained from wild-type and Crem knock-out mouse testis.
2012-04-11 | GSE29593 | GEO
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In adrenal glands it is involved in the regulation of expression of genes for steroid hormone synthesis. In this dataset, we include the expression data obtained from wild-type and Crem knock-out mouse adrenal glands.
2014-05-25 | GSE29592 | GEO
Project description:CREM (cAMP responsive element modulator) together with CREB and ATF-1 belong to the CREB family of transcriptional factors, that respond to cyclic AMP signaling and bind to cAMP responsive element (CRE) sites in promoters of selected genes. CREM can produce isoforms that have either activating or repressing functions, depending on the transcription of specific exons. In this dataset, we include the expression data obtained from wild-type (WT) and Crem knock-out (KO) mouse liver. Several comparisons were made. KO<WT at 0h, KO<WT at 12 h, 0h<12h in WT and 0h<12h in KO.
2014-05-25 | GSE29594 | GEO
Project description:A characteristic feature of allergic diseases is the appearance of a subset of CD4+ cells known as TH2 cells, which is controlled by transcriptional and epigenetic mechanisms. We aimed to analyze the role of CREM, a known transcriptional activator of T cells, with regard to TH2 responses and allergic diseases in men and mice. Here we demonstrate that T cells of asthmatic children and PBMCs of adults with atopy express lower mRNA levels of the transcription factor CREM compared to cells from healthy controls. CREM deficiency in murine T cells results in enhanced TH2 effector cytokines in vitro and in vivo and CREM-/- mice demonstrate stronger airway hyperresponsiveness in an OVA-induced asthma model. Mechanistically, both direct CREM binding to the IL-4 and IL-13 promoter as well as a decreased IL-2 dependent STAT5 activation suppress the TH2 response. Accordingly, mice selectively overexpressing CREMα in T cells display decreased TH2 type cytokines in vivo and in vitro, and are protected in an asthma model. Thus, we provide evidence that CREM is a negative regulator of the TH2 response and determines the outcome of allergic asthma.
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Project description:Testis brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport, stabilization, and storage. Targeted inactivation of TB-RBP leads to abnormalities in fertility and behavior. A testis-enriched kinesin KIF17b coimmunoprecipitates with TB-RBP in a RNA-protein complex containing specific cAMP-responsive element modulator (CREM)-regulated mRNAs. The specificity of this interaction is confirmed by in vivo RNA-protein crosslinking and transfections of hippocampal neurons. Combining in situ hybridization and immunohistochemistry at the electron microscope level, a temporally sequential dissociation of KIF17b and TB-RBP from specific mRNAs is detected with TB-RBP release coincident with the time of mRNA translation, indicating a separation of the processes of transport and translation. We conclude that KIF17b serves as a molecular motor component of a TB-RBP-mouse ribonucleoprotein complex transporting a group of specific CREM-regulated mRNAs in mammalian male postmeiotic germ cells. Because KIF17b has been reported to control CREM-dependent transcription in male germ cells by regulating the intracellular location of the transcriptional coactivator activator of CREM in testis, this indicates that one kinesin links the processes of transcription and transport of specific mRNAs in mammalian male germ cells.
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Project description:In the liver, group 1 innate lymphoid cells (ILCs) comprise 10–20% tissue-resident ILC1 cells and 80–90% conventional NK cells. Both cells contribute to early defense against virus infection by secreting IFN-γ. However, the distinct role of ILC1 cells in viral infections remains incompletely understood. Here, we identified that ILC1 cells outnumbered NK cells, constituting 80–90% of group 1 ILCs in the liver during undernutrition. Mechanistically, undernutrition significantly reduced NK cell numbers, while hepatic ILC1 cells entered a quiescent state that allowed them to survive in an mTORC1-dependent manner. Metabolically, quiescent ILC1 cells exhibited greater glucose uptake than NK cells and efficiently utilized it via oxidative phosphorylation, which was induced by mTORC1. Finally, ILC1-deficient mice succumbed to MCMV infection under undernourished conditions, but not when fed ad libitum. These findings suggest a non-redundant function of hepatic ILC1 cells in protecting the host against MCMV infection during undernutrition.
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