Mouse single positive thymocyte bulk RNA-seq from Kmt2d knockout and control littermates.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA844331 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To evaluate the hypothesis that dysregulated thymocyte development contributes to immune deficiencies in individuals with KS1. We generated bulk murine CD4+ or CD8+ single positive thymocyte RNA-seq data from cells which lack the histone methyltransferase, Kmt2d SET domain (exons 50/51), with a conditional Cre-recombinase driven by Lck-CreMar (T cell specific) or Vav1-iCre (hematopoietic). Expression profiling by high throughput sequencing.
2024-05-03 | GSE205285 | GEO
Project description:Somatic mutations in various epigenetic regulators, including histone methyltransferases KMT2C and KMT2D, have emerged as important cancer-driving events. However, the mechanism of action and therapeutic vulnerability imparted by these mutations remain poorly understood. We identified KMT2D and 8 other epigenetic regulators as potential suppressors to melanoma initiation through an in vivo pooled epigenome-focused RNAi screen. Loss of KMT2D, which exhibits somatic mutations in human melanoma and other cancers, drastically enhanced melanoma progression in xenograft models and a BRAFV600E-driven genetically engineered mouse model of melanoma. Epigenome profiling of 6 histone marks and chromatin state alterations showed substantial reprogramming of H3K4me1- and H3K27ac-marked active enhancer states in KMT2D mutant tumors. Energy metabolic pathways such as glycolysis, OxPhos and TCA/electron transport showed high degree of deregulation which was confirmed with metabolic profiling. Pharmacological abrogation of glycolysis led to reduced proliferation and tumorigenesis preferentially in KMT2D mutant cells. Mechanistically, we find that enhancer loss at IGFBPs increases IGF signaling and downstream AKT phosphorylation that leads to upregulation of metabolic pathways rendering KMT2D mutant cells dependent on these energy metabolism pathways for their higher growth potential. Overall, we present evidence that KMT2D mutations promote tumorigenesis by reprogramming energy metabolism pathways through enhancer reprogramming.
2020-11-16 | GSE116852 | GEO
Project description:Somatic mutations in various epigenetic regulators, including histone methyltransferases KMT2C and KMT2D, have emerged as important cancer-driving events. However, the mechanism of action and therapeutic vulnerability imparted by these mutations remain poorly understood. We identified KMT2D and 8 other epigenetic regulators as potential suppressors to melanoma initiation through an in vivo pooled epigenome-focused RNAi screen. Loss of KMT2D, which exhibits somatic mutations in human melanoma and other cancers, drastically enhanced melanoma progression in xenograft models and a BRAFV600E-driven genetically engineered mouse model of melanoma. Epigenome profiling of 6 histone marks and chromatin state alterations showed substantial reprogramming of H3K4me1- and H3K27ac-marked active enhancer states in KMT2D mutant tumors. Energy metabolic pathways such as glycolysis, OxPhos and TCA/electron transport showed high degree of deregulation which was confirmed with metabolic profiling. Pharmacological abrogation of glycolysis led to reduced proliferation and tumorigenesis preferentially in KMT2D mutant cells. Mechanistically, we find that enhancer loss at IGFBPs increases IGF signaling and downstream AKT phosphorylation that leads to upregulation of metabolic pathways rendering KMT2D mutant cells dependent on these energy metabolism pathways for their higher growth potential. Overall, we present evidence that KMT2D mutations promote tumorigenesis by reprogramming energy metabolism pathways through enhancer reprogramming.
2020-11-16 | GSE116851 | GEO
Project description:RNA-seq data from double positive thymocyte and CD4 or CD8 single positive spleen T cell
| PRJNA448448 | ENA
Project description:RNA-seq of KMT2D Knockout and KMT2D WT melanoma in mice
| PRJNA480453 | ENA
Project description:Microarray experiment with whole thymi from genetically enginereed mice, with purified thymocyte samples and with cell lines.
2004-06-30 | E-MEXP-96 | biostudies-arrayexpress
Project description:Histone methyltransferase KMT2D is epigenetic modifier mediates histone H3 lysine 4 methylation (H3K4me) with distinct roles across different cancer types. We previous found that KMT2D promotes growth and metastasis in Androgen receptor (AR)-negative prostate cancer (PCa). However, the functions of KMT2D and the relationship with AR in AR-positive prostate cancer remain unclear. Here, we showed that inhibition of KMT2D reduced AR-positive PCa cell survival and the sensitivity to dihydrotestosterone, a ligand for AR. RNA-Seq analysis revealed that KMT2D suppression significantly attenuated AR signaling pathway. Through multiple-omics analysis, we revealed that KMT2D recruits pioneering transcription factor Forkhead box A1 (FOXA1) to AR-specific enhancer sites, induces open chromatin conformations, and facilitates AR binding at enhancers to activate downstream gene expression, ultimately leading to AR reactivation. KMT2D knockout by CRISPR/Cas9 reduced CRPC tumor growth and AR signaling pathway activation in vivo. KMT2D-FOXA1-AR axis also mediates ketone metabolic reprogramming by regulating the expression of the key enzyme HMGCS2 to promote PCa progression. Finally, targeting UTX, a member of complex of proteins associated with SET1 (COMPASS) in which KMT2D involved, suppressed PCa cell survival and tumor growth by impairing H3K4me1 modification via KMT2D. These findings demonstrate the oncogenic role of KMT2D in PCa, suggesting that blocking COMPASS to inhibition KMT2D’s function may be a promising strategy to treat PCa.
2025-02-01 | GSE285692 | GEO
Project description:Histone methyltransferase KMT2D is epigenetic modifier mediates histone H3 lysine 4 methylation (H3K4me) with distinct roles across different cancer types. We previous found that KMT2D promotes growth and metastasis in Androgen receptor (AR)-negative prostate cancer (PCa). However, the functions of KMT2D and the relationship with AR in AR-positive prostate cancer remain unclear. Here, we showed that inhibition of KMT2D reduced AR-positive PCa cell survival and the sensitivity to dihydrotestosterone, a ligand for AR. RNA-Seq analysis revealed that KMT2D suppression significantly attenuated AR signaling pathway. Through multiple-omics analysis, we revealed that KMT2D recruits pioneering transcription factor Forkhead box A1 (FOXA1) to AR-specific enhancer sites, induces open chromatin conformations, and facilitates AR binding at enhancers to activate downstream gene expression, ultimately leading to AR reactivation. KMT2D knockout by CRISPR/Cas9 reduced CRPC tumor growth and AR signaling pathway activation in vivo. KMT2D-FOXA1-AR axis also mediates ketone metabolic reprogramming by regulating the expression of the key enzyme HMGCS2 to promote PCa progression. Finally, targeting UTX, a member of complex of proteins associated with SET1 (COMPASS) in which KMT2D involved, suppressed PCa cell survival and tumor growth by impairing H3K4me1 modification via KMT2D. These findings demonstrate the oncogenic role of KMT2D in PCa, suggesting that blocking COMPASS to inhibition KMT2D’s function may be a promising strategy to treat PCa.
2025-02-01 | GSE285691 | GEO
Project description:Control RNA-seq data for thymocyte and spleen T cell.
2019-03-31 | GSE112609 | GEO
Project description:DBC1 is a positive regulator of enhancer epigenomic writers KMT2D and p300
| PRJNA743890 | ENA