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SRP050076
Mus musculus
33 Downloadable Samples
Illumina HiSeq 2000
Description
Unrestrained receptor tyrosine kinase (RTK) signaling and epigenetic deregulation are root causes of tumorigenesis. We establish linkage between these processes by demonstrating that aberrant RTK signaling unleashed by oncogenic HRasG12V or loss of negative feedback through Sprouty gene deletion remodels histone modifications associated with active typical and super-enhancers. However, while both lesions disrupt the Ras-Erk axis, the expression programs, enhancer signatures, and transcription factor networks modulated upon HRasG12V-transformation or Sprouty deletion are largely distinct. Oncogenic HRasG12V elevates histone 3 lysine 27 acetylation (H3K27ac) levels at enhancers near the transcription factor Gata4 and the kinase Prkcb, as well as their expression levels. We show that Gata4 is necessary for the aberrant gene expression and H3K27ac marking at enhancers, and Prkcb is required for the oncogenic effects of HRasG12V-driven cells. Taken together, our findings demonstrate that dynamic reprogramming of the cellular enhancer landscape is a major effect of oncogenic RTK signaling. Overall design: We assessed gene expression changes upon loss of feedback regulation through Sprouty (Spry) deletion, and upon unrestrained signaling driven by mutant oncogenes. RNA-seq was performed in biological triplicate; replicate number is included in the sample name. Spry124fl/fl (VEC) and Spry124-/- (CRE) MEFs were profiled in three conditions: unsynchronized (U), serum starved (S), and serum starved and FGF treated (F). Spry124fl/fl (VEC) MEFs transduced with empty vector (EV) control or the indicated oncogenes (KRasG12V, HRasG12V, and BRafV600E) as well as Spry124-/- (CRE) MEFs transduced with EV control were profiled in the unsynchronized state.
Publication Title
Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
In this project we analyze the transcriptome of the human multiple myeloma isogenic cell lines ARP-1 (UTX wild-type) and ARD (UTX null). The transcriptome is studied at baseline, upon restoration of UTX levels in ARD cells for 3 and 6 days, and upon treatment of the cell lines with the EZH2 inhibitor GSK343. Moreover, we analyzed the transcriptome of a ARD resistant cell line that we generated. Overall design: Examination of transcriptome of two cell lines upon restoration of UTX and treatment with EZH2 inhibitors
Publication Title
UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
We investigated differential gene expression in response to treatment of multiple myeloma cells with EZH2 inhibitor Overall design: RNA-seq in two cell lines
Publication Title
Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation.
Sample Metadata Fields
No sample metadata fields
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