JMJD2B is expressed in a high proportion of human breast tumors, and the expression levels significantly correlate with estrogen receptor (ER) positivity. To assess the effect of JMJD2B depletion on the ER signaling pathway, we performed genome-wide gene expression analysis using the Affymetrix Human Gene 1.0 ST array.
Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.
Sex, Specimen part, Cell line, Treatment
View SamplesTransforming growth factor (TGF)- plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF--induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF--induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
Specimen part
View SamplesDNA methylation has been considered to play an important role during myogenic differentiation. In terminal differentiation of myoblasts, chronological alteration of DNA methylation status was poorly understood. Using Infinium HumanMethylation450 BeadChips, we validated genome wide DNA methylation profiles of human myoblast differentiation models. To investigate correlation between DNA methylation and gene expression, we also assessed gene expression of myoblasts with GeneChip Human Genome U133 Plus 2.0 array.
DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation.
Sex, Age, Race
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Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesEach fraction of mouse hematopoietic cells was purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and its gene expression was analyzed.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesMouse CD34(-)KSL hematopoietic stem cells and CD34(+)KSL multipotent progenitors were purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and their gene expression was analyzed.
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Specimen part
View SamplesBmi1 is a component of polycomb repressive complex 1 and its role in the inheritance of the stemness of adult somatic stem cells has been well characterized. Bmi1 maintains the self-renewal capacity of adult stem cells, at least partially, by repressing the Ink4a/Arf locus that encodes a cyclin-dependent kinase inhibitor, p16Ink4a, and a tumor suppressor, p19Arf 14. Deletion of both Ink4a and Arf in Bmi1-deficient mice substantially restored the defective self-renewal capacity of HSCs and neural stem cells.
Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes.
Specimen part
View SamplesTo understand molecular mechanisms by which JunB regulates Treg function, we performed RNA-seq analysis of JunB-deficient and control Treg cells (CD4+ CD25hi). Overall design: Gene expresson profiles in WT and JunB-deficient Treg cells.
JunB regulates homeostasis and suppressive functions of effector regulatory T cells.
Specimen part, Cell line, Subject
View SamplesThe polycomb group (PcG) proteins function in gene silencing through histone modifications. They form chromatin-associated multiprotein complexes, termed polycomb repressive complex (PRC) 1 and PRC2. These two complexes work in a coordinated manner in the maintenance of cellular memories through transcriptional repression of target genes. EZH2 is a catalytic component of PRC2 and trimethylates histone H3 at lysine 27 to transcriptionally repress the target genes. PcG proteins have been characterized as general regulators of stem cells, but recent works also unveiled their critical roles in cancer.
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.
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A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
Specimen part, Cell line, Treatment
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