Similar Datasets
Project description:Investigations of the roles of epigenetic regulator KAT2A in ccRCC
| PRJNA739744 | ENA
Project description:The SAGA transcriptional co-activator complex regulates gene expression through histone acetylation at promoters, mediated by its histone acetyl transferase, KAT2A. While its structure and function have been extensively investigated, how the stability of individual subunits of SAGA, including KAT2A, is regulated, remains unclear. Here, using a fluorescence-based KAT2A stability reporter, we systematically dissect the molecular dependencies controlling KAT2A protein abundance. We identify the non-enzymatic SAGA CORE module subunits—TADA1, TAF5L, and TAF6L— as necessary for KAT2A stability, with loss of these subunits disrupting the integrity of SAGA, leading to non-chromatin-bound KAT2A that is degraded by the proteasome, consequently leading to reduced H3K9 acetylation. Proteomic profiling reveals progressive loss of CORE and HAT components upon acute disruption of the SAGA CORE, indicating that an intact CORE is required for the stability of numerous components of SAGA. Finally, a focused CRISPR screen of ubiquitin-proteasome system genes identifies the E3 ligase UBR5, a known regulator of orphan protein degradation, and the deubiquitinase OTUD5, as regulators of KAT2A degradation when the SAGA CORE is perturbed. Together, these findings reveal a dependency of KAT2A protein stability on SAGA CORE integrity and define an orphan quality control mechanism targeting unassembled KAT2A, revealing a potential vulnerability in SAGA-driven malignancies.
2026-03-16 | GSE300600 | GEO
Project description:We sequenced mRNA from 24 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine transcriptome and the first CA1-transcriptome in response to environmental novelty under normal and Kat2a-loss-of-function conditions. Samples were divded in 4 groups: A: Control naM-CM-/ve (n=6), B: control novelty-exposed (n=5), C: Kat2a cKO naM-CM-/ve (n=6), D: Kat2a cKO novelty-exposed (n=7). Pairwise comparisons for AvsB, AvsC, BvsD and CvsD were performed using DESeq2.
2014-07-16 | E-GEOD-53380 | biostudies-arrayexpress
Project description:We sequenced small RNAs from 12 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine miRNome under normal and Kat2a-loss-of-function conditions. Samples were divded in 4 groups: A: Control (n=6), C: Kat2a cKO naïve (n=6)
2014-07-16 | E-GEOD-53427 | biostudies-arrayexpress
Project description:Identification of histone acetylation targets of Kat2a activity in murine models of acute myeloid leukaemia (AML) driven by the MLL-AF9 oncogenic fusion
2020-02-03 | GSE118768 | GEO
Project description:Identification of histone acetylation targets of Kat2a activity in murine models of acute myeloid leukemia (AML) driven by the MLL-AF9 oncogenic fusion
2020-02-03 | GSE118576 | GEO
Project description:Chemerin is an oncogenic adipokine in ccRCC, and signals through CMKLR1 or GPR1 receptors. In order to determine the gene expression pathways controlled by chemerin (RARRES2), and what each receptor does, we knockout the three genes in 769-P ccRCC cells and performed RNAseq.
2024-04-11 | E-MTAB-14016 | biostudies-arrayexpress
Project description:KAT2A is a histone acetyl-transferase involved in stabilization of transcriptional activity through acetylation of lysine residue 9 of Histone 3. Mouse knockout models suggest that Kat2a is dispensable for haematopoietic stem and progenitor cell activity, despite a central role in survival and maintenance of Acute Myekoid Leukaemia cells through block of differentiation. Herein, we investigate KAT2A activity in human cord blood haematopoiesis and identify a specific requirement in the establishment of the erythroid lineage. KAT2A is required for specification and survival of Erythroid-Megakaryocytic progenitors, with regulation of expression of the erythropoietin receptor (EPOR) gene, which participates in lineage commitment, as well as of later effector genes in the platelet and erythroid lineages. Early and late lineage roles can be distinctly attributed to the ATAC and SAGA complexes in which context KAT2A exerts its activity. ATAC is active earlier in erythroid lineage development and mediates MEP specification from HSC, whilst SAGA activity is required post-commitment, including in expression of haemoglobin genes. We thus position KAT2A as a novel regulator of human erythropoiesis and separate early and later effects in lineage development with complex specificity. This has implications for putative therapeutic targeting of KAT2A complexes in leukaemia.
2021-09-28 | GSE128512 | GEO
Project description:KAT2A is a histone acetyl-transferase involved in stabilization of transcriptional activity through acetylation of lysine residue 9 of Histone 3. Mouse knockout models suggest that Kat2a is dispensable for haematopoietic stem and progenitor cell activity, despite a central role in survival and maintenance of Acute Myekoid Leukaemia cells through block of differentiation. Herein, we investigate KAT2A activity in human cord blood haematopoiesis and identify a specific requirement in the establishment of the erythroid lineage. KAT2A is required for specification and survival of Erythroid-Megakaryocytic progenitors, with regulation of expression of the erythropoietin receptor (EPOR) gene, which participates in lineage commitment, as well as of later effector genes in the platelet and erythroid lineages. Early and late lineage roles can be distinctly attributed to the ATAC and SAGA complexes in which context KAT2A exerts its activity. ATAC is active earlier in erythroid lineage development and mediates MEP specification from HSC, whilst SAGA activity is required post-commitment, including in expression of haemoglobin genes. We thus position KAT2A as a novel regulator of human erythropoiesis and separate early and later effects in lineage development with complex specificity. This has implications for putative therapeutic targeting of KAT2A complexes in leukaemia.
2021-09-28 | GSE128902 | GEO
Project description:The mammalian epidermis undergoes constant renewal replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology orchestrated, in part, by epigenetic modifiers. Here, we defined the role of histone acetyltransferase KAT2A in epidermal homeostasis and provided a comparative analysis that revealed key functional divergence with its paralogue, KAT2B. In contrast to KAT2B's reported function in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whilst loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N-terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B- mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes utilize a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.
2023-06-09 | GSE215244 | GEO