Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1004894 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25621479_1.fastq.gz | Fastqsanger.gz | |||
| SRR25621479_2.fastq.gz | Fastqsanger.gz | |||
| SRR25621480_1.fastq.gz | Fastqsanger.gz | |||
| SRR25621480_2.fastq.gz | Fastqsanger.gz | |||
| SRR25621481_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The lysine acetyltransferase KAT6A epigenetically facilitates glucose metabolic programming and CD4+ T-cell responses in autoimmunity
| PRJNA1006399 | ENA
Project description:Epigenetic programs are pivotal regulators of effector CD4+ T cells and determine the fate of many autoimmune disorders. Here, we show that the acetyltransferase KAT6A acts as a novel regulator of glucose metabolism that is required for the proliferation and effector functions of CD4+ T cells in autoimmunity. Clinical analysis shows that KAT6A in CD4+ T cells is linked to the progression of autoimmune Sjogren’s syndrome (SS) . Conditional knockout of KAT6A inhibits the proliferation and Th1/Th17 effector functions of CD4+ T cells both in vitro and that KAT6A-cKO CD4+T cells are less susceptible to induce adjuvant-immunized experimental autoimmune encephalomyelitis (EAE), autoimmune colitis and experimental SS. Combination of metabolomic, epigenetic and transcriptomic analyses show that KAT6A maintains abundant acetylation of H3K9ac and H3K27ac sites of several glycolytic genes, which in turn disrupts the transcriptional activation of MYC and HIF-1α, and potentiates the metabolic programming of glycolysis through its enzymatic amino acid points. Treatment with KAT6A small-molecule inhibitors in various autoimmune mice models shows high therapeutic value for targeting KAT6A to the treatment of autoimmune disorders. Our study reveals a critical role for KAT6A in autoimmunity via the epigenetic modification of glucose metabolic reprogramming and the effector response of CD4+ T cells.
2023-12-09 | GSE241099 | GEO
Project description:The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrated that a winged helix domain at the N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A to unmethylated CpG islands (CGIs) genome wide. Mutation of the essential amino acids completely abrogates the enrichment of KAT6A at CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases
2023-01-14 | PXD034833 | Pride
Project description:We have previously demonstrated that a ketogenic diet alleviates cardiac pathology under high blood pressure. Here we show that lysine acetyltransferase 6A (KAT6A) is acetylated in the hearts of mice fed a ketogenic diet under hypertension, which enhances its interaction with AMPK regulatory subunits. RNA-sequencing analysis demonstrated that the KAT6A-K815Q acetylation-mimetic mutant stimulates AMPK signaling in cardiomyocytes. Moreover, the KAT6A-K815Q acetylation-mimetic mutant mitigated phenylephrine-induced mitochondrial dysfunction and cardiomyocyte hypertrophy via AMPK activation in vitro.
2025-12-02 | GSE286926 | GEO
Project description:The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing haematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the haematopoietic system. We found that KAT6B sustained the fetal haematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished haematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating haematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg and Flt3. In conclusion, we identified the haematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.
2024-02-25 | GSE256039 | GEO
Project description:The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.
2022-12-20 | GSE206272 | GEO
Project description:The lysine acetyltransferase KAT6A (MOZ, MYST3) belongs to the MYST family of chromatin regulators, facilitating histone acetylation. Dysregulation of KAT6A has been implicated in developmental syndromes and the onset of acute myeloid leukemia (AML). Previous work suggests that KAT6A is recruited to its genomic targets by a combinatorial function of histone binding PHD fingers, transcription factors and chromatin binding interaction partners. Here, we demonstrate that a winged helix (WH) domain at the very N-terminus of KAT6A specifically interacts with unmethylated CpG motifs. This DNA binding function leads to the association of KAT6A with unmethylated CpG islands (CGIs) genome-wide. Mutation of the essential amino acids for DNA binding completely abrogates the enrichment of KAT6A at CGIs. In contrast, deletion of a second WH domain or the histone tail binding PHD fingers only subtly influences the binding of KAT6A to CGIs. Overexpression of a KAT6A WH1 mutant has a dominant negative effect on H3K9 histone acetylation, which is comparable to the effects upon overexpression of a KAT6A HAT domain mutant. Taken together, our work revealed a previously unrecognized chromatin recruitment mechanism of KAT6A, offering a new perspective on the role of KAT6A in gene regulation and human diseases.
2022-12-20 | GSE206273 | GEO
Project description:Aberrant SMAD3 activation has been implicated as a driving event in cancer metastasis. However, the drivers of SMAD3 activation are poorly defined. Here, we identify SMAD3 as a non-histone substrate of lysine acetyltransferase 6A (KAT6A). The acetylation of SMAD3 at K20 and K117 by KAT6A with promotes SMAD3 association with oncogenic H3K23ac reader TRIM24 and upregulation of immune response-related cytokines. This event in turn leads to enhanced myeloid-derived suppressor cell (MDSC) recruitment and triple-negative breast cancer (TNBC) metastasis. Inhibiting KAT6A in combination with anti-PD-L1 therapy in treating breast cancer xenograft-bearing animals markedly attenuates TNBC metastasis and provides a significant survival benefit. Thus, our work presents an KAT6A acetylation-dependent regulatory mechanism governing SMAD3 oncogenic function and provides insight into how targeting an epigenetic factor with immunotherapies enhances the anti-metastasis efficacy.
2021-11-03 | GSE171230 | GEO
Project description:Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo truncating mutations in the gene KAT6A (Lysine(K) acetyltransferase 6A). ARTHS is clinically heterogeneous but characterized by several common features including intellectual disability, developmental and speech delay, hypotonia, congenital heart defects and gastrointestinal problems. KAT6A mRNA is highly expressed throughout early development and the levels of expression are lower levels in differentiated tissues, suggesting a key role maintenance of the stem cell characteristics. Across these cell types, the gene-regulatory mechanisms controlled by KAT6A and the histone-acetylation complex in which it works remain unknown. In this study, we created ARTHS patient-derived (n=7) and control (n=13) dermal fibroblasts from skin punch biopsies. KAT6A is expressed at moderate levels in human fibroblast cells and we performed a comprehensive profiling of the epigenomic and transcriptomic changes in ARTHS.
2023-08-15 | GSE237022 | GEO
Project description:Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo truncating mutations in the gene KAT6A (Lysine(K) acetyltransferase 6A). ARTHS is clinically heterogeneous but characterized by several common features including intellectual disability, developmental and speech delay, hypotonia, congenital heart defects and gastrointestinal problems. KAT6A mRNA is highly expressed throughout early development and the levels of expression are lower levels in differentiated tissues, suggesting a key role maintenance of the stem cell characteristics. Across these cell types, the gene-regulatory mechanisms controlled by KAT6A and the histone-acetylation complex in which it works remain unknown. In this study, we created ARTHS patient-derived (n=7) and control (n=13) dermal fibroblasts from skin punch biopsies. KAT6A is expressed at moderate levels in human fibroblast cells and we performed a comprehensive profiling of the epigenomic and transcriptomic changes in ARTHS.
2023-08-15 | GSE237021 | GEO