Background: 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (DMHF) is one of the major odor compounds generated by the Maillard reaction. We previously reported that the inhalation of DMHF decreased systolic blood pressure via the autonomic nervous system in rats. The autonomic nervous system is also closely related to appetite regulation. The present study investigated the effects of DMHF on dietary intake and gene expression.
DMHF (2,5-dimethyl-4-hydroxy-3(2H)-furanone), a volatile food component generated by the Maillard reaction, promotes appetite and changes gene expression in the rat brain through inhalation.
Sex, Age, Specimen part, Treatment
View SamplesThe molecular mechanism responsible for cell fate after mitotic slippage is unclear. We investigate the postmitotic effects of different mitotic aberrations, misaligned chromosomes produced by CENP-E siRNA (siCENP-E), and monopolar spindles resulting from Eg5 siRNA (siEg5).
Expression data of HeLa cells treated with CENP-E siRNA or Eg5 siRNA in the presence of BubR1 siRNA.
Cell line
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 SamplesAnti-angiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma (HCC); however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human HCC cells by long-term treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin 4 (T4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones. Highlighting epigenetic alterations involved in drug resistance, we revealed that T4 could be aberrantly expressed following demethylation of DNA and active modification of histone H3 at the promoter region. Ectopic overexpression of T4 in HCC cells could significantly enhance sphere-forming capacities and infiltrating phenotypes in vitro, and promote growth of tumors refractory to the VEGFR mutltikinase inhibitor sorafenib in vivo. Clinically, sorafenib failed to improve the progression-free survival in patients with T4-high HCC, indicating that T4 expression could be available as a surrogate marker of susceptibility to this drug. This study suggests that T4 expression triggered by epigenetic alterations could contribute to the development of resistance to anti-angiogenic therapy by the acquisition of stemness, and that epigenetic control might be one of the key targets to regulate the resistance in HCC.
Acquired Resistance with Epigenetic Alterations Under Long-Term Antiangiogenic Therapy for Hepatocellular Carcinoma.
Specimen part, Cell line
View SamplesPlant vascular tissues are essential for the existence of land plants. Many studies have revealed the process underlying the development of vascular tissues. However, the initiation of vascular development is still a mystery. LONESOME HIGHWAY (LHW), which encodes a bHLH transcription factor, is expressed in the initial step of vascular development in roots. LHW and TMO5 LIKE1 (T5L1) interact each other and function as a heterodimer. Here, we identified specific genes downstream of LHW-T5L1 with transformed suspension culture cells in microarray experiments.
A bHLH complex activates vascular cell division via cytokinin action in root apical meristem.
Specimen part, Treatment, Time
View SamplesCircadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the post-transcriptional regulation of Clock subsequent to the cellular differentiation for the emergence of robust circadian clock oscillation in mouse fetal hearts and mESCs (mouse embryonic stem cells). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable in around embryonic day (E) 10 whereas robust oscillation was clearly visible in E18 heart. Temporal RNA-seq analysis using mouse fetal hearts reveals much fewer rhythmic genes in E10-12 hearts (63, no clock genes) than E17-19 (483 genes), indicating the lack of functional circadian clocks in E10 mouse fetal hearts. In both mESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was at least partially due to miRNA-mediated translational suppression of CLOCK. The CLOCK protein is required for the robust molecular oscillation in differentiated cells, and the post-transcriptional regulation of Clock plays a key role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.
Involvement of posttranscriptional regulation of <i>Clock</i> in the emergence of circadian clock oscillation during mouse development.
No sample metadata fields
View SamplesGene expression data from mouse organs after hydroxypropyl--cyclodextrin injection
Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen.
Sex, Specimen part
View SamplesHepatocyte nuclear factor-4 (HNF4, NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4 in the steady state remains to be elucidated. Here we report the native HNF4 isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4 and Hepatocyte nuclear factor-4 was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4 and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation.
Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.
Specimen part, Cell line
View SamplesHepatocyte nuclear factor-4 (HNF4, NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4 in the steady state remains to be elucidated. Here we report the native HNF4 isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4 and Hepatocyte nuclear factor-4 was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4 and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation.
Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors.
Specimen part, Cell line
View SamplesWe used microarrays to determine global gene expression in primary tumor tissues (ESCC) and matched normal tissues (adjacent normal esophageal mucosa)
Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis.
Sex, Age, Specimen part
View Samples