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SRP144212
Homo sapiens
56 Downloadable Samples
Illumina HiSeq 2500
Description
While activation of canonical NF-?B signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-?B pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin ß receptor (LTßR)- and FN14-dependent p52 nuclear translocation, but not TNFa receptor (TNFR)-mediated, canonical NF-?B p65 nuclear translocation. Chemoproteomics identified cyclin dependent kinase 12 (CDK12) as the target of 919278. CDK12 inhibition by 919278, THZ1, or siRNA knock down all affect similar global transcriptional changes and prevent LTßR and FN14-dependent MAP3K14 (NIK) mRNA induction and subsequent protein accumulation. In addition, 919278 and THZ1 treatment reduce RNA Pol II CTD phosphorylation. This powerful approach of coupling a phenotypic screen with chemoproteomics revealed a novel regulatory pathway of the non-canonical NF-?B pathway that could serve as a therapeutic target in autoimmunity and cancer. Overall design: There are TWEAK stimulated and unstimulated conditions, 4hr and 24hr time points. 7 treatments (DMSO, BIO0702697, BIO0919278, BIO032202, NTsiRNA, siRNAs523626, siRNAs523629) in duplicates. In total, 56 sample were sequenced and analyzed.
Publication Title
CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
We present key transcription factors (TFs) and transcriptional regulatory networks (TRNs) delineating how they control cellular processes related to the SSC reprogramming.
Publication Title
Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed an mRNA-sequencing experiment using Drosophila midgut to find uracil-induced signaling pathways and biological processes in response to uracil. The sequenced reads from Illumina Hiseq2000 that passed quality filters were mapped to Drosophila genome (NCBI build 5.3) using Tophat and then quantitatively analyzed by HTseq at the gene level. By comparing uracil-treated and non-treated samplesl, we profiled uracil-dependent gene expression changes. Overall design: mRNA expression profiles of uracil-treated Drosophila midgut and control Drosophila midgut were examined by Illumina Hiseq2000.
Publication Title
Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The actions of transcription factors, chromatin modifiers, and noncoding RNAs are crucial for the programming of cellular states. Although chromatin remodeling factors regulate the functional status of cells including pluripotency and differentiation, how they cross-talk with embryonic stem (ES) cell-specific transcription factors and noncoding RNAs to coordinate networks controlling of ES cell identity remain unknown. Here, we find that Pontin chromatin remodeling factor plays an essential role as a coactivator for Oct4 target genes and large intergenic noncoding RNAs (lincRNAs) in ES cells. mRNA- and ChIP-sequencing analyses reveal that Pontin and Oct4 share a substantial set of target genes involved in maintenance of ES cells. Intriguingly, Oct4-dependent coactivator function of Pontin extends to transcription of lincRNAs that are mainly involved in repression of differentiation in ES cells. Together, our findings demonstrate newly identified Oct4-Pontin-lincRNA module plays critical roles in the ES cell circuitry to orchestrate cell fate determination program. Overall design: For mRNA-sequencing, we obtained mRNAs from 1) Pontinf/f; CreER ES cells at 0, 3, or 4 days post-treatment with 4-hydroxy tamoxifen (OHT) for Pontin-depleted ES cells without biological replicates (n=1), 2) ZHBTc4 ES cells at 2 days post-treatment with tetracycline (Tc) for Oct4-depleted ES cells (n=1), and 3) ZHBTc4 ES cells infected by pLKO control or pLKO-shlinc1253 lentivirus at 4 days post infection for knockdown of linc1253 (n=2). For ChIP-sequencing, chromatin extracts containing DNA fragments with an average size of 400bp were immmunoprecipitated by using antibodies against GFP (control) or Pontin. Eluted ChIP DNA (n=1).
Publication Title
Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The retinoic acid receptor-related orphan receptor a (RORa) is a member of the NR1 subfamily of orphan nuclear hormone receptors. RORa is an important regulator of various biological processes, including cerebellum development, cancer and circadian rhythm. To determine molecular mechanism by which hepatic deletion of RORa induces obesity and insulin resistance, we performed global transcriptome analysis from high-fat diet (HFD)-fed RORa f/f and RORa LKO mouse liver tissues. This analysis provides insight into molecular mechanisms for RORa in high-fat-diet condition. Overall design: mRNA expression profiles of RORa f/f and RORa LKO mice liver with control diet or high-fat-diet were examined by Illumina HiSeq 2500.
Publication Title
RORα controls hepatic lipid homeostasis via negative regulation of PPARγ transcriptional network.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 1500
Description
We performed an mRNA-sequencing experiment using ZIP10 positive and negative cells isolated from the ventral skins of WT mice and analyzed gene expression profiles of those cells to identify the functional differences between the two cell types. Overall design: ZIP10 positive and negative cells from the ventral skins of one-week-old WT mice were sorted by flow cytometry. From those cells, we isolated mRNAs and analyzed gene expression profiles by mRNA sequencing.
Publication Title
Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples