YY1 is a ubiquitously expressed transcription factor that has been demonstrated to be essential for pro-B cell development. However, the role of YY1 in other B cell populations has never been investigated. It has been proposed that YY1 is a key regulator for the germinal center B cell program since the YY1 motif was present in much higher frequency in germinal center B cell signature genes than signature genes of other B cell subsets. Indeed, in accord with this prediction, we demonstrated that deletion of YY1 by Cg1-Cre completely prevented differentiation of naïve B cells into germinal center B cells and plasma cells after antigen stimulation. To determine if YY1 was also required for the differentiation of other B cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B cell subsets including B1 B cells require YY1 for their differentiation. By deleting YY1 acutely with ER-Cre, we demonstrated that all B cell subsets require YY1 for their maintenance. ChIP-seq shows that YY1 predominantly binds to promoters, and pathway analysis of the genes which bind YY1 show that they are enriched in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription, such as mRNA splicing, metabolism of RNA. By RNA-seq analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, while it normally downregulates genes involved in transcription, mRNA splicing, NF-kB signaling pathways, AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, cell proliferation and c-Myc targets. Overall design: Total RNA was prepared from RAG-/-pro-B cells, RAG-/-YY1f/f x mb1-Cre pro-B cells, RAG-/- µ+ pre-B cells, C57BL/6 follicular B cells, and C57BL/6 GC B cells. RNA was extracted using TRIzol (Life Technologies) and genomic DNA was eliminated using the genomic DNA wipeout buffer in the QuantiTect Reverse transcription kit (Qiagen). A final purification of the RNA was performed with the RNeasy kit (Qiagen). Ribosomal RNA was eliminated using Ribo-Zero Magnetic Gold Kit (Illumina).RNA samples were submitted to the Next Generation Sequencing Core, where they were processed with the NEBNext Ultra Directional RNA Library Prep Kit for Illumina and sequenced on the Illumina HiSeq. Three independent RNA-seq samples were used for RAG-/- pro-B and RAG-/- YY1f/f x mb1-Cre pro-B cells, and two samples for the other cell types.
YY1 plays an essential role at all stages of B-cell differentiation.
Sex, Specimen part, Cell line, Subject
View SamplesInhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of PDE10A activity would have significant effects on gene expression in the striatum. A comparison of the expression profile of PDE10A knockout (KO) mice and wild-type mice after chronic PDE10A inhibition revealed altered expression of 19 overlapping genes with few significant changes outside the striatum or after administration of a PDE10A inhibitor to KO animals. Chronic inhibition of PDE10A produced up-regulation of mRNAs encoding genes that included prodynorphin, synaptotagmin10, phosphodiesterase 1C, glutamate decarboxylase 1, and diacylglycerol O-acyltransferase and a down-regulation of mRNAs encoding choline acetyltransferase and Kv1.6, suggesting long-term suppression of the PDE10A enzyme is consistent with altered striatal excitability and potential utility as a antipsychotic therapy. In addition, up-regulation of mRNAs encoding histone 3 (H3) and down-regulation of histone deacetylase 4, follistatin, and claspin mRNAs suggests activation of molecular cascades capable of neuroprotection. We used lentiviral delivery of cAMP response element (CRE)-luciferase reporter constructs into the striatum and live animal imaging of 2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid (TP-10)-induced luciferase activity to further demonstrate PDE10 inhibition results in CRE-mediated transcription. Consistent with potential neuroprotective cascades, we also demonstrate phosphorylation of mitogen- and stress-activated kinase 1 and H3 in vivo after TP-10 treatment. The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease.
Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease.
Specimen part, Treatment
View SamplesThe goal of this study was to examine whether immune responses to Plasmodium chabaudi infection differ between the sexes and are altered by the presence of gonadal steroids. Gonadally-intact males were more likely than intact females to die following P. chabaudi infection, exhibit slower recovery from infection-associated weight loss, hypothermia, and anemia, have reduced IFN-associated gene expression and IFN production during peak parasitemia, and produce less antibody during the recovery phase of infection. Gonadectomy of male and female mice altered these sex-associated differences, suggesting that sex steroid hormone, in particular androgens and estrogens, may modulate immune responses to infection.
Involvement of gonadal steroids and gamma interferon in sex differences in response to blood-stage malaria infection.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part, Time
View SamplesTo determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression.
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part
View SamplesIdentification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
No sample metadata fields
View SamplesIdentification of genes differentially expressed in tumorigenic compared to non-tumorigenic, HPV18 positive cells
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
No sample metadata fields
View SamplesWe used microarrays to detail the global gene expression changes following RNAi knock-down of dTip60 in Drosophila SL2 cells
Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60.
Cell line
View SamplesOf the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA
Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
No sample metadata fields
View SamplesGene expression profiles were examined in whole lung tissue collected from male and female Long-Evans rats at different time points after inoculation with Seoul virus (i.e., the species-specific hantavirus that infects Norway rats)
Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats.
No sample metadata fields
View Samples