Ctr9 knockdown in mouse ES cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12078 | GEO | 2008/07/18
SECONDARY ACCESSION(S): PRJNA113335
REPOSITORIES: GEO
Similar Datasets
Project description:To monitor global transcript changes after Paf1C depletion we transfected ESCs with esiRNA targeting Ctr9 and control esiRNA (Luc). Experiment Overall Design: 4 replicates of esiRNA tranfection controls (luciferase esiRNA) and 4 replicates of Ctr9 esiRNA tranfection samples
2008-10-21 | E-GEOD-12078 | biostudies-arrayexpress
Project description:To study the function of Paf1C in mouse ESCs, we generated an ES cell line stably expressing a location and affinity purification (LAP)-tagged Ctr9 fusiuon protein using the bacterial astificial chromosome (BAC)-based TransgeneOmics approach. To investigate whether pluripotency and lineage control genes differentially regulated upon Paf1C depletion are direct targets of the Paf1C, we analyzed the binding of the Ctr9-LAP fusion protein by ChIP-chip and identified 2175 promoter regions that were bound by Ctr9. The supplementary bed file contains promoter regions bound by Ctr9. Keywords: ChIP-chip
2009-01-31 | GSE14654 | GEO
Project description:Project Abstract : Paf1C is a general transcription regulator and is associated with various human diseases. One of its subunits, CTR9, is known as a structurally and functionally core component of Paf1C. While its role in higher eukaryotes have been researched, the association between the core component and human fungal pathogen is not fully understood yet. During pre-infection process, Candida albicans adheres to the surface of hosts and sufficiently grows as the circular form. Under immune deficiency condition, C. albicans enters into the infection process and forms hyphae. Here, we performed virulence tests and transcriptome analysis to identify the role of CTR9 in two infection stages. In pre-infection process, CTR9 regulates basic cellular processes and metabolism, affecting cell growth. Of metabolic processes, methionine biosynthetic genes are significantly dependent on CTR9. This pathway hardly affects cell abundance for pre-infection stage, but has considerable effect on hyphal formation during infection stage. Therefore, it shows that methionine biosynthetic pathway mediated by CTR9 is essential for pathogenesis of C. albicans.
2023-11-30 | GSE244665 | GEO
Project description:Compare the gene expression profiles of ESCs stably expressing control and KIAA1718 short hairpin RNA, using Affymetrix microarray. Mouse ES cells R1 were transformed with the respective lenti-virus expressing Luc shRNA or KIAA1718 shRNA1. The transformed ES cells were sorted for GFP. Total RNAs were extracted from cells using Trizol reagent (Invitrogen, Carlsbad, CA). For microarray experiments, RNA was processed and hybridized to Mouse Genome 430 2.0 arrays (Affymetrix) according to the manifacture’s instruction.
2009-11-03 | E-GEOD-18771 | biostudies-arrayexpress
Project description:Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), has been demonstrated as a positive regulator of ERα-positive breast cancer progression and ERα-target gene expression. Previously, we found that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at select ERα-target genes. However, the genome-wide regulation of the occupancy of ERα and RNAPII mediated by Ctr9 is still unclear. Here, we determined the genome-wide ERα and RNAPII occupancy in response to estrogen induction and/or Ctr9 knockdown by performing chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). We found that loss of Ctr9 dramatically decreases the global occupancy of ERα and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ERα-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ERα and Ctr9 target genes, and further delineates the possible independent function of Ctr9 from other subunits in PAFc.
2016-10-10 | GSE80728 | GEO
Project description:CTR9 is the scaffold subunit in PAFc (Polymerase associated factor complex), a multifunctional complex employed in multiple steps of RNA Pol II-mediated transcription. CTR9/PAFc is well known as an evolutionarily conserved elongation factor regulating gene activation via coupling with histone modifications enzymes. However, little is known about its function to restrain repressive histone markers. Using inducible and stable CTR9 knockdown breast cancer cell lines, we discovered that the amount of H3K27me3 is strictly controlled by CTR9. Quantitative profiling on histone modifications revealed a striking increase of H3K27me3 level upon loss of CTR9. Moreover, loss of CTR9 leads to genome-wide expansion of H3K27me3, as well as increased recruitment of PRC2 on chromatin, which can be reversed by CTR9 restoration. Moreover, CTR9 depletion triggers a PRC2 subtype switch from less active PRC2.2 to PRC2.1 with higher methyltransferase activity. As a consequence, CTR9 depletion generates vulnerability that renders breast cancer cells hypersensitive to PRC2 inhibitors. Our findings that CTR9 demarcates PRC2-mediated H3K27me3 levels and genomic distribution provide a unique mechanism of transition from transcriptionally active to repressive chromatin states and shed light on the biological functions of CTR9 in development and cancer.
2021-10-19 | GSE173176 | GEO
Project description:In pancreatic ductal adenocarcinoma (PDAC), MYC is required for S-phase progression and escape from immune surveillance. Here we show that recruitment of the PAF1c transcription elongation complex to RNA polymerase depends on MYC and that depletion of CTR9, a PAF1c subunit, enables long-term survival of PDAC-bearing mice. PAF1c is largely dispensable for unperturbed proliferation and regulation of MYC target genes. Instead, PAF1c limits DNA damage associated with transcription-replication conflicts by being essential for expression of long DNA repair genes. Surprisingly, the survival benefit conferred by CTR9 depletion is not due to DNA damage, but to restoration of immune surveillance. This occurs because CTR9 depletion releases RNA polymerase and the histone chaperone SPT6 from the body of long genes, promoting transcription of short genes that include MHC class-I genes. The data show that functionally distinct gene sets compete for elongation factors and directly link MYC-driven S-phase progression to tumor immune evasion.
2024-01-01 | GSE228797 | GEO
Project description:In pancreatic ductal adenocarcinoma (PDAC), MYC is required for S-phase progression and escape from immune surveillance. Here we show that recruitment of the PAF1c transcription elongation complex to RNA polymerase depends on MYC and that depletion of CTR9, a PAF1c subunit, enables long-term survival of PDAC-bearing mice. PAF1c is largely dispensable for unperturbed proliferation and regulation of MYC target genes. Instead, PAF1c limits DNA damage associated with transcription-replication conflicts by being essential for expression of long DNA repair genes. Surprisingly, the survival benefit conferred by CTR9 depletion is not due to DNA damage, but to restoration of immune surveillance. This occurs because CTR9 depletion releases RNA polymerase and the histone chaperone SPT6 from the body of long genes, promoting transcription of short genes that include MHC class-I genes. The data show that functionally distinct gene sets compete for elongation factors and directly link MYC-driven S-phase progression to tumor immune evasion.
2024-01-01 | GSE228795 | GEO
Project description:In pancreatic ductal adenocarcinoma (PDAC), MYC is required for S-phase progression and escape from immune surveillance. Here we show that recruitment of the PAF1c transcription elongation complex to RNA polymerase depends on MYC and that depletion of CTR9, a PAF1c subunit, enables long-term survival of PDAC-bearing mice. PAF1c is largely dispensable for unperturbed proliferation and regulation of MYC target genes. Instead, PAF1c limits DNA damage associated with transcription-replication conflicts by being essential for expression of long DNA repair genes. Surprisingly, the survival benefit conferred by CTR9 depletion is not due to DNA damage, but to restoration of immune surveillance. This occurs because CTR9 depletion releases RNA polymerase and the histone chaperone SPT6 from the body of long genes, promoting transcription of short genes that include MHC class-I genes. The data show that functionally distinct gene sets compete for elongation factors and directly link MYC-driven S-phase progression to tumor immune evasion.
2024-01-01 | GSE228799 | GEO
Project description:Cell-fate determination of human mesenchymal stem/stromal cells (hMSCs) is precisely regulated by lineage-specific transcription factors and epigenetic enzymes. We found that CTR9, a key scaffold subunit of Polymerase Associated Factor Complex (PAFc), selectively regulates hMSC differentiation to osteoblasts and chondrocytes, but not to adipocytes. An in vivo ectopic osteogenesis assay confirmed the essentiality of CTR9 in hMSC-derived bone formation. CTR9 counteracts the activity of EZH2, the epigenetic enzyme that deposits H3K27me3, in hMSCs. Accordingly, CTR9 knockdown (1) hMSCs gain H3K27me3 mark, and the osteogenic differentiation defects of CTR9 KD hMSCs can be partially rescued by treatment with EZH2 inhibitors. Transcriptome analyses identified Bone Morphology Protein-2 (BMP-2) as a downstream effector of CTR9. BMP-2 secretion, membrane anchorage, as well as the BMP-SMAD pathway were impaired in CTR9 KD MSCs, and the effects were rescued by BMP-2 supplementation. This study uncovers an epigenetic mechanism engaging CTR9-H3K27me3-BMP-2 axis to regulate osteochondral lineage differentiation of hMSCs. To investigate the function of CTR9 in the gene regulation of early osteogenic committment , we established human MSCs in which CTR9 gene has been knocked down by two individual shRNAs (shControl vs shCTR9#3/#5）.
2022-11-23 | GSE213277 | GEO