Sulforaphane (SFN), an isothiocyanate, is part of an important group of naturally occurring small molecules with antiinflammatory properties. Even though the published reports are vague, most are best conceivable with an inhibition of T cell functions. We therefore analyzed the effect of SFN on T cell-mediated autoimmune disease. Feeding mice with SFN protected from severe experimental autoimmune encephalomyelitis (EAE). Disease amelioration was associated with reduced interleukin (IL)-17 and IFN-gamma expression in draining lymph nodes. In vitro, SFN treatment of T cells did not directly alter T cell cytokine secretion. In contrast, SFN treatment of dendritic cells (DC) inhibited TLR4-induced IL-12 and IL-23 production and the cytokine profile of T cells stimulated by SFN-treated DC. SFN suppressed TLR4-induced nuclear factor kappa B (NFB) activity, without affecting the degradation of its inhibitor (IB). Instead, SFN treatment of DC resulted in strong expression of the stress response protein heme oxygenase-1 (HO-1), which interacts with NFB p65 and inhibits its activity. Consistent with these findings, HO-1 bound to p65 and subsequently inhibited the p65 promoter activity within the IL23a and IL12b promoter region. Importantly, SFN suppressed Il23a and Il12b expression in vivo and silenced Th17/Th1 responses within the CNS . Our data show that SFN improves Th17/Th1-mediated autoimmune disease by inducing HO-1 and inhibiting p65-regulated IL-23 and IL-12 expression.
Sulforaphane protects from T cell-mediated autoimmune disease by inhibition of IL-23 and IL-12 in dendritic cells.
Specimen part, Treatment
View SamplesTo determine the effects of depleting TIP60, CDK8, or HIF1A on the transcriptional response to hypoxia, we performed RNAseq analysis of four HCT116 colorectal carcinoma cell lines (shNT, HIF1A-/-, shTIP60 and shCDK8) in normoxic and hypoxic (24hrs, 1% O2) conditions. Overall design: PolyA RNA for two independent biological replicates was purified from HCT116 cells stably expressing an shRNA against a non-targeting control (shNT), TIP60 (shTIP60) or CDK8 (shCDK8), or genetically deleted HIF1A (HIF1A-/-) subjected to 24hrs 1% O2 (hypoxia) or maintained under ambient oxygen (21%; normoxia) was sequenced on the Ion Torrent platform. Reads were aligned to the human genome and gene-level counts were used for differential expression analysis.
The TIP60 Complex Is a Conserved Coactivator of HIF1A.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.
Cell line, Treatment
View SamplesHCT116 microarray done 12 hours after treatment with DMSO (control) or Nutlin
Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.
Cell line, Treatment
View SamplesEtiolated Arabidopsis seedlings open their cotyledons and halt rapid elongation of hypocotyl when exposed to light (de-etiolation). Major light responsive components in this process have been identified and signaling pathways revealed, yet how the organ-specific light responses are achieved remains unknown. Here we report that a developmental regulator TCP4 (TEOSINTE BRANCHED1, CYCLOIDEA, and PCF) participates in photomorphogenesis and facilitates light-induced cotyledon-opening. We demonstrate that TCP4-like transcriptional factors, which predominantly express in cotyledons of both light and dark seedlings, activate SAUR16 and SAUR50 in response to light. Light repressor PIF3 (or PIFs, phytochrome-interacting factors), which accumulates in etiolated seedlings and rapidly declines upon light exposure, inhibits TCP4 promoter-binding and prevents activation of SAUR16/50 in darkness. Our study reveals how an interplay between light responsive factors and developmental regulators leads to signal-dependent and tissue-specific regulation of gene expressions, which ultimately resulted in organ-specific light responses during de-etiolation. Overall design: Cotyledon mRNA profiles of 4-day-old dark grown Col, mTCP4#4 and mTCP4#10 seedlings were generated by deep sequencing.
The Transcription Factors TCP4 and PIF3 Antagonistically Regulate Organ-Specific Light Induction of <i>SAUR</i> Genes to Modulate Cotyledon Opening during De-Etiolation in Arabidopsis.
Specimen part, Subject
View SamplesDrosophila males double transcription of their single X chromosome to equalize X-linked gene expression with females, which carry two X chromosomes. Increased transcription requires the Male-Specific Lethal (MSL) complex. One of the primary functions of the MSL complex is thought to be enrichment of H4Ac16 on the male X chromosome, a modification linked to elevated transcription. The roX1 and roX2 RNAs are essential but redundant components of the MSL complex. Simultaneous removal of both roX RNAs reduces MSL X-localization and leads to ectopic binding of these proteins at autosomal sites and to the chromocenter. Some H4Ac16 accumulates at these ectopic sites in roX1- roX2- males, suggesting the possibility of increased expression. The global effect of roX mutations on gene expression was measured by microarray analysis. We found that expression of the X chromosome was decreased by 26% in roX1- roX2- male larvae, supporting the involvement of roX RNAs in the up-regulation of X-linked genes. This finding is broadly comparable to reports of reduced X chromosome expression following msl2 RNAi knockdown in S2 cells. In spite of strong MSL binding and H4Ac16 accumulation at autosomal sites in roX1- roX2- males, enhanced gene expression could not be detected at these sites by microarray analysis or reverse northern blotting. Thus, failure to compensate X-linked genes, rather than inappropriate up-regulation of autosomal genes at ectopic sites of MSL binding, appears to cause male lethality upon loss of roX RNAs.
roX RNAs are required for increased expression of X-linked genes in Drosophila melanogaster males.
Sex
View SamplesThe origin of biological samples (In vitro infection of HCT-8 cells with Cryptosporidium parvum)
Cryptosporidium parvum regulation of human epithelial cell gene expression.
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View SamplesATH1 GeneChip was used for gene expression analysis of wild-type plants and dor mutant under drought treatment (both the wild-type and dor plants were grown under normal watering conditions for 24 days and then stressed by completely depriving of irrigation for 10 days). Two biological repeat experiments were conducted and the raw data was analyzed applying Affymetrix GCOS software.
F-box protein DOR functions as a novel inhibitory factor for abscisic acid-induced stomatal closure under drought stress in Arabidopsis,.
No sample metadata fields
View SamplesThe CDKN2A/B locus at 9p21.3 contains crucial tumor suppressors (P16, P14, and P15) and oncogenic lncRNA ANRIL genes. This locus is most frequently inactivated in cancer genomes by deletion and DNA methylation. However, the mechanisms coordinately regulating their expression level are far from clear. In the present study, a novel lncRNA, P14AS, was characterized in the antisense strand of the fragment near CDKN2A in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq). Overall design: RNAs were characterized in the antisense strand of the fragment near CDKN2A in human cell lines using CDKN2A-specific probe captured RNA-sequencing (RNACap-Seq).
Characterization of novel LncRNA P14AS as a protector of ANRIL through AUF1 binding in human cells.
Specimen part, Cell line, Subject
View SamplesIn the diploid genome, genes come in two copies, which can have different DNA sequence and where one is maternal and one is paternal. In a particular cell, a gene could potentially be expressed from both copies (biallelic expression) or only one (monoallelic). We performed RNA-Sequencing on individual cells, from zygote to the cells of the late blastocyst, and also individual cells from the adult liver. Using first generation crosses between two distantly related mouse strains, CAST/Ei and C57BL/6, we determined the expression separately from the maternal and paternal alleles. We found that half of the genes were expressed by only one allele, randomly so that some cells would express the paternal allele, some the maternal and a few cell both alleles. We also observed the spread of the progressive inactivation of the paternal X chromosome. Overall design: First generation mouse strain crosses were used to study monoallelic expression on the single cell level
Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
No sample metadata fields
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