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Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [ChIP-seq]

ABSTRACT: Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [ChIP-seq]

PROVIDER: PRJNA1040744 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26834844_1.fastq.gz	Fastqsanger.gz
	SRR26834844_2.fastq.gz	Fastqsanger.gz
	SRR26834845_1.fastq.gz	Fastqsanger.gz
	SRR26834845_2.fastq.gz	Fastqsanger.gz
	SRR26834846_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [RNA-Seq]

Project description:Histone lysine lactylation is a physiologically relevant epigenetic pathway that can be stimulated by the Warburg effect and L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-CoA, the cofactor for the modification, and how this process is regulated remain unknown. Here we report identification of GTPSCS as a robust lactyl-CoA synthetase using biochemistry and cell biology approaches. The mechanism of this catalytic activity was elucidated using the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to form a functional lactyltransferase to elevate histone lactylation, but not histone succinylation. This process is dependent on not only a nuclear localization signal in the GTPSCS G1 subunit, but also acetylation at G2 subunit residue K73 which mediates the interaction with p300. GTPSCS-p300 collaboration synergistically regulates histone H3K18la, subsequently enhancing the expression of GDF15. This process promotes the proliferation of glioma cells and facilitates tumor formation in mice. In addition, GTPSCS is upregulated in glioma and correlates with glioma malignancy, while histone H3K18la, and GDF15 levels are positively associated with glioma malignancy and poor prognosis in GBM patients. The GTPSCS-lactyltransferase-histone Kla axis thus represents an epigenetic pathway linking lactate metabolism with an oncogenic gene expression pattern in glioma.

2024-11-26 | GSE248703 | GEO

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [ChIP-seq]

2024-11-26 | GSE247800 | GEO

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation

Project description:Histone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect and L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-CoA, the cofactor for the modification, and how this process is regulated remain unknown. Here we report identification of GTPSCS as a lactyl-CoA synthetase in the nucleus using biochemistry and cell biology approaches. The mechanism of this catalytic activity was elucidated using the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to form a functional lactyltransferase to elevate histone lactylation, but not histone succinylation. This process is dependent on not only a nuclear localization signal in the GTPSCS G1 subunit, but also acetylation at G2 subunit residue K73 which mediates the interaction with p300. GTPSCS-p300 collaboration synergistically regulates histone H3K18la, subsequently enhancing the expression of GDF15. This process promotes the proliferation and radioresistance of gliomas. The GTPSCS represents the inaugural enzyme that can catalyze lactyl-CoA synthesis for epigenetic histone lactylation and regulate oncogenic gene expression patterns in glioma.

2024-12-02 | PXD056791 | Pride

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression

Project description:Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression

| PRJNA1045615 | ENA

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [RNA-Seq]

Project description:Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression [RNA-Seq]

| PRJNA1045624 | ENA

Nuclear GTPSCS functions as a lactyl-CoA ligase to promote histone lactylation and glioma progression

Project description:Histone lysine lactylation is a physiologically relevant epigenetic pathway that can be stimulated by the Warburg effect and hypoxia-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-CoA, the cofactor for the modification, and how this process is regulated remain unknown. Here, we report the identification of GTPSCS as a lactyl-CoA ligase using biochemistry and cell biology approaches. The mechanism of this catalytic activity was elucidated using the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to form a functional lactyltransferase to elevate histone H3 lysine 18 lactylation (H3K18la). This process is dependent on not only a nuclear localization signal in the GTPSCS G1 subunit but also acetylation at the G2 subunit residue K73 (for the interaction between GTPSCS and p300). GTPSCS-p300-mediated histone H3K18la promotes glioma cell proliferation and tumor formation in mice. In addition, histone H3K18la is positively associated with glioma grade and poor prognosis in glioma patients. The LDHA-GTPSCS-lactyltransferase-histone Kla axis thus represents a signal-stimulated epigenetic pathway that mediates the downstream impact of the Warburg effect and hypoxia

2024-12-04 | PXD037672 | Pride

PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis

Project description:Longstanding evidence implicates glioma stem cells (GSCs) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we demonstrated that global lactylation was significantly elevated in GSCs compared to differentiated glioma cells (DGCs). PTBP1, a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced its RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.

2024-11-05 | GSE262995 | GEO

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and glioma progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-26 | GSE248704 | GEO

Acetyl-CoA synthetase 2: a critical linkage in obesity-induced tumorigenesis in myeloma

Project description:Acetyl-CoA synthetase 2: a critical linkage in obesity-induced tumorigenesis in myeloma

| PRJNA548531 | ENA

Succinyl-CoA synthetase deficiency in mouse forebrain results in hyper-succinylation with perturbed neuronal transcriptional regulation and metabolism (ATAC-Seq)

Project description:Lysine-succinylation is a subtype of protein acylation associated with metabolic regulation of succinyl-CoA in the TCA cycle. Deficiency of succinyl-CoA synthetase (SCS), the TCA-cycle enzyme catalyzing the reversible conversion of succinyl-CoA to succinate, leads to mitochondrial encephalomyopathy in humans and embryonic lethality in mice. This report presents a conditional forebrain-specific knock-out (KO0 mouse model of Sucla2, the gene encoding the ATP-specific beta isoform of SCS, resulting in postnatal deficiency of the entire SCS complex. Results demonstrate that the accumulation of succinyl-CoA in the absence of SCS leads to hyper-succinylation within the cerebral cortex of adult mice. With previous research identifying succinylation marks on histones, and with proteomic evidence of histone lysine-succinylation within the presented model, global chromatin accessibility was surveyed in Sucla2 mutant and control mice via ATAC-sequencing. Data show wide-scale alterations in chromatin landscape and global gene expression. Computational analysis of combined chromatin-accessibility and gene expression data reveal perturbation of neuronal transcriptional regulatory networks in the mutant forebrain, suggesting SCS-related changes in the protein succinylome and chromatin accessibility play a significant role in the neuronal pathogenesis of SCS-deficiency.

2022-07-27 | GSE208690 | GEO

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