The transcription factor c-MYC intron binding protein 1 (MIBP1) binds to various genomic regulatory regions, including intron 1 of c-MYC. This factor is highly expressed in post-mitotic neurons in the fetal brain and may be involved in various biological steps, such as neurological and immunological processes. In this study, we globally characterized the transcriptional targets of MIBP1 and proteins that interact with MIBP1. Microarray hybridization followed by Gene Set Enrichment Analysis revealed that genes involved in the pathways downstream of MYC, NF-B, and TGF- were downregulated when HEK293 cells stably overexpressed MIBP1. In silico transcription factor binding site analysis of the promoter regions of these downregulated genes showed that the NF-B binding site was the most overrepresented. The upregulation of genes known to be in the NF-B pathway after the knockdown of endogenous MIBP1 in HT1080 cells supports the view that MIBP1 is a downregulator of the NF-B pathway. We also confirmed the binding of the MIBP1 to the NF-B site. By immunoprecipitation and mass spectrometry, we detected O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT) as a prominent binding partner of MIBP1. Analyses using deletion mutants revealed that a 154-amino acid region of MIBP1 was necessary for its OGT binding and O-GlcNAcylation. A luciferase reporter assay showed that NF-B-responsive expression was repressed by MIBP1, and stronger repression by MIBP1 lacking the 154-amino acid region was observed. Our results indicate that the primary effect of MIBP1 expression is the downregulation of the NF-B pathway, and that this effect is attenuated by O-GlcNAc signaling.
Genome-wide repression of NF-κB target genes by transcription factor MIBP1 and its modulation by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase.
Cell line
View SamplesWe performed global scale microarray analysis to identify detailed mechanisms by which nonpermissive temperature induces cell growth arrest and differentiation in astrocyte RCG-12 cells harboring temperature-sensitive simian virus 40 large T-antigen by using an Affymetrix GeneChip system. Astrocyte RCG-12 cells used in this study were derived from primary cultured rat cortical glia cells infecting with a temperature-sensitive simian virus 40 large T-antigen. Although the cells grew continuously at the permissive temperature, the nonpermissive temperature led to cell growth arrest and differentiation. Of the 15,923 probe sets analyzed, nonpermissive temperature differentially expressed 556 probe sets by >2.0-fold.
Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line RCG-12.
No sample metadata fields
View SamplesTAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms.
Transcriptional coactivator with PDZ-binding motif is essential for normal alveolarization in mice.
No sample metadata fields
View SamplesLactic acid bacteria confer a variety of health benefits. Here we investigate the mechanisms by which Lactobacillus brevis KB290 enhances cell-mediated cytotoxic activity. We fed a diet containing KB290 (3 10^9 colony-forming units/g) , or potato starch, to 9-week-old female BALB/c mice for 1, 4, 7, or 14 days and examined the cytotoxic activity of splenocytes was measured. RNA was extracted from the spleen and analyzed for gene expression by DNA microarray.
Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.
Sex, Age, Specimen part
View SamplesPersistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Cell line
View SamplesiPSC-derived NSPCs, which were induced by two different protocols (Embryoid body or Neural rosette) followed by expansion in free-floating culture (neurospheres), had closely resembled profiles.
Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.
Sex, Race
View SamplesThe entire small intestine was obseved by balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.
Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease.
Specimen part, Disease, Disease stage
View SamplesWe have previously established an in vitro tissue culture system (named VISUAL; Kondo et al., 2016), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
BES1 and BZR1 Redundantly Promote Phloem and Xylem Differentiation.
Specimen part, Treatment, Time
View SamplesXylem consists of three types of cells: vessel cells, also referred to as tracheary elements (TEs), parenchyma cells, and fiber cells. TE differentiation includes two essential processes, programmed cell death (PCD) and secondary cell wall formation. These two processes are tightly coupled. However, little is known about the molecular mechanism of their gene regulation. Here, we show that VASCULAR-RELATED NAC-DOMAIN 6 (VND6), a master regulator of TEs, regulates these processes in a coordinated manner. We first identified specific genes downstream of VND6 by comparing them with those of SECONDARY WALL-ASSOCIATES NAC DOMAIN PROTEIN1 (SND1), a master regulator of xylem fiber cells, with transformed suspension culture cells in microarray experiments.
Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 directly regulates the genes that govern programmed cell death and secondary wall formation during xylem differentiation.
Time
View SamplesMED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-dependent target genes; however, the genes in this subset varies between cell types. MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown. We generated Med23 conditional knockout mice and induced Med23 deletion in early T cell development using the lineage specific Lck-Cre transgene. While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T cell master regulatory transcription factor. Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects. Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression. In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2.
T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs.
Sex, Specimen part
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