Histone methylation is a complex posttranslational modification regulating transcription and chromatin dynamics, and plays important roles in development and disease processes. Recent studies indicate that histone lysine methylation is a reversible modification and several JmjC-domain-containing proteins have been identified as histone lysine demethylases. Here we show that KIAA1718, a JmjC-domain-containing protein, is a histone demethylase. KIAA1718 demethylated dimethylation of H3 lysine 9 and 27 (H3K9me2 and H3K27me2), two important epigenetic marks associated with embryonic development6-10. In mouse embryonic stem cells (ESCs), KIAA1718 expression increased at the early phase of neural differentiation. RNA interference inhibition of KIAA1718 blocked neural differentiation and the effect was rescued by wild-type human gene, but not by a catalytically inactive mutant. In chick embryos, KIAA1718 is exclusively expressed in the epiblast cells of the primitive streak, an organizer contributing to neural induction. Knockdown of KIAA1718 resulted in defects in neural formation, while its overexpression led to neural expansion. The pro-neural effect is mediated through transcriptional activation of FGF4, a growth factor implicated in neural induction. Thus, our study identifies a dual specific histone demethylase as a novel epigenetic factor integrated with growth factor signaling, which has important roles in the early neural development.
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Specimen part, Cell line
View SamplesCompare the gene expression profiles of ESCs stably expressing control and KIAA1718 short hairpin RNA, using Affymetrix microarray.
No associated publication
Specimen part, Cell line
View SamplesWe reasoned that the pi-RISC, by virtue of the enormous sequence portfolio of piRNAs, might mediate elimination of a large variety of mRNAs in late stages of spermiogenesis. Both Miwi-null and Caf1-null mice showed early spermiogenic arrest, preventing us from determining the role of MIWI and CAF1 in elongating spermatids using the existing genetic models.
Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis.
Specimen part
View SamplesZygotic genome activation (ZGA), which is according to the midblastula transition in zebrafish, is an important event during the maternal-zygotic transition in animals. Our preliminary study and other groups works indicate that epigenetic regulations play an essential role in ZGA.
Protein Arginine Methyltransferase 6 (Prmt6) Is Essential for Early Zebrafish Development through the Direct Suppression of gadd45αa Stress Sensor Gene.
Age, Specimen part
View SamplesDCs treated with PTX (PTX-DC) is able to induce EAE like PTX as adjuvant whereas neither LPS nor DCs treated with LPS (LPS-DC) fails to induce EAE. We want to identify genes that are responsible for EAE induction in DCs and genes that are able to toloerize EAE in DCs through the microarray.
No associated publication
Specimen part, Treatment
View SamplesK-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the Ras-addiction of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer.
Selective requirement for Mediator MED23 in Ras-active lung cancer.
Specimen part, Cell line
View SamplesCD4+ helper T cells are critical for immunological response. Th2 cells, a subset of CD4+ helper T cells, are responsible for asthma and other immune diseases. We found a Th2 secreted protein, ExtraCellular Matrix protein 1 (ECM1), which is highly induced by classic IL-4 signaling pathway during helper T cells differentiation.
ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1).
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View SamplesInnate immunity is the first line of defense against viral and microbial pathogens. BMDC is critical for innate immunity. To investigate the complicated net signaling after virus invasion, we did a cDNA microarray analysis of BMDC with or without Sendai Virus infection. We used microarrays to find proteins that upregulated by Sendai Virus infection and investigated if these proteins had functions in regulating Sendai Virus induced signaling pathway.
Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors.
Specimen part
View SamplesHere we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally-distant lineage (fibroblasts) into induced hematopoietic progenitors (iHPs). We analyzed transcriptomic data for cell undergoing the transdifferentiation process at several time-points of the process.
Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors.
Specimen part
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