Differential gene expression analysis upon Kat7 deletion in mouse lung AT2 cells [bulk RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1290214 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenomic dysregulation is widespread in cancer. However, the specific epigenomic regulators and the processes they control to drive cancer phenotypes are poorly understood. We employed a novel, scalable and high-throughput in vivo method to perform iterative functional screens of >250 epigenomic regulators within autochthonous oncogenic KRAS-driven lung tumors. We identified many previously unappreciated epigenomic tumor-suppressor and tumor-dependency genes. We show that a specific HBO1 complex and MLL1 complex are robust tumor suppressors in lung cancer. Histone modifications generated by HBO1 complex are frequently reduced in human lung adenocarcinomas and is associated with worse clinical features. HBO1 and MLL1 complexes co-occupy shared genomic regions, impacting chromatin accessibility, expression of canonical tumor suppressor genes and lineage fidelity. The HBO1 complex is epistatic with the MLL1 complex and other tumor suppressor genes in lung adenocarcinoma development. Together, these results uncover the HBO1 and MLL1 complexes as critical functional modules in restraining lung adenocarcinoma development and provide a in vivo phenotypic roadmap of epigenomic regulators in lung tumorigenesis.
2025-09-05 | GSE302346 | GEO
Project description:Differential Gene Expression Upon PFN1 Deletion
| PRJNA630391 | ENA
Project description:Carnitine palmitoyltransferase 1a (CPT1a) is the key regulator of mitochondrial long-chain fatty acid beta-oxidation (LCFAO). However, the functional significance of AT2 cell-specific LCFAO at baseline and during acute lung injury (ALI) is not fully understood. In this study, Murine models of AT2 cell-specific Cpt1a deletion were generated for investigating the role of CPT1a in regulating AT2 cell function and the severity of lipopolysaccharide-induced murine ALI models.
2024-07-05 | GSE255949 | GEO
Project description:To investigate the proteins bound to KAT7 in response to DNA damage, we harvested and extracted proteins after treating HCT116 with etoposide. The KAT7 protein and its binding protein were immunoprecipitated using KAT7-specific antibodies and analyzed by mass spectrometry. The mass spectra provided clues to study the function of KAT7 during DNA damage stress.
2024-12-12 | PXD043664 | Pride
Project description:Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 cell identity are unknown. Here we show that the E26 transformation-specific (ETS) family transcription factor Etv5 is essential tomaintain AT2 cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I (AT1) cells. Consistent with a defect in the AT2 stem cell population, Etv5 deficiency markedly reduced recovery following bleomycin-induced lung injury. Lung tumorigenesis driven by mutant KrasG12D was also compromised by Etv5 deficiency. ERK activation downstream of Ras was found to stabilize Etv5 through inactivation of the cullin- RING ubiquitin ligase CRL4COP1/DET1 that targets Etv5 for proteasomal degradation. These findings identify Etv5 as a critical output of Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation.
2018-03-08 | GSE111569 | GEO
Project description:Tissue-specific deletion of the gene encoding the histone acetyltransferase Kat7 (Hbo1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation, and a failure to express the neuronal differentiation program. Proliferating neural stem and progenitor cells (NPSCs) were isolated from Kat7-deleted and Kat7-intact 14.5 day embryonic mouse fetuses.
2022-12-09 | GSE220498 | GEO
Project description:To identify the acylation modification site of KAT7 in response to DNA damage, we treated HCT116 cells with etoposide, extracted proteins and purified KAT7 protein with KAT-specific antibodies for mass spectrometry analysis.This mass spectrometry identified the level of acylation modification of KAT7 in response to DNA damage in HCT116 cell line.
2024-12-12 | PXD043707 | Pride
Project description:Transcriptome of ESCs upon MLL1 inhibition/deletion
| PRJNA420025 | ENA
Project description:Thymic epithelial cells (TECs) govern thymic T lymphocyte differentiation and selection. Medullary TECs are distinctive for their "promiscuous" gene expression, transcribing thousands of peripheral tissue genes (PTG) that are otherwise only expressed highly in one or two other organs. Much of this PTG expression by mTECs is controlled by the autoimmune regulator, AIRE. This experiment was part of a larger study in which we examined the impact of Kat7 loss on AIRE-mediated PTG expression. Despite the apparently normal differentiation of AIRE+ TECs in Kat7-knockout mice, it was possible that the defect in AIRE-mediated PTG expression was secondary to the developmental loss of this histone acetyltransferase. To address this hypothesis, we employed fetal thymic organ cultures (FTOC) depleted of thymocytes where AIRE+ mTEC and PTG expression was induced by an agonist anti-RANK antibody. We then used two different approaches to acutely block KAT7 function and subsequently sort purified TECs for RNA-seq analysis to assess the impact on AIRE-mediated PTG transcription. AIRE+ mTECs exhibit relatively low turnover in organ culture; therefore, this approach uncouples KAT7 impacts on AIRE function from potential influences on TEC differentiation. Our first approach employed a new small molecule inhibitor of KAT7 function, WM-3835. The second approach was an inducible genetic deletion system. FTOC established with thymi from control (Kat7fl/fl) or RosaCre-ERT2 Kat7fl/fl mice were treated with tamoxifen to activate CRE-mediated deletion of Kat7.
2021-12-21 | GSE188869 | GEO
Project description:Tissue specific deletion of the gene encoding the histone acetyltransferase KAT7 (HBO1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation and a failure to express the neuronal differentiation program. KAT7 genome occupancy and histone H3 lysine 14 acetylation (H3K14ac) levels were assessed by ChIP-seq in proliferating Kat7 deleted vs. Kat7 intact neural stem and progenitor cells (NSPCs). KAT7 and H3K14ac were completely absent in the Kat7 deleted cells. IN KAT7 intact cells, KAT7 occupancy levels and H3K14ac levels within the body of genes correlated strongly and positively. Both were higher in genes that were expressed strongly than in genes with lower or no expression. However, KAT7 and H3K14ac were present in all genes including silent genes and in all other regions of the genome, including intergenic regions and regions decorated with histone H3 lysine 9 trimethylation (H3K9me3), an indicator of constitutive heterochromatin.
2022-11-30 | GSE216459 | GEO