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RNA-seq analysis of BRD4 knockdown in U937 cells

ABSTRACT: Succinyl-CoA synthetase was reported to sustain mitochondrial respiration and enhance leukemia proliferation. However, the biological mechanisms of mitochondrial metabolism and leukemia pathogenesis, beyond energy production, remains underexplored. Here we report that depletion of SUCLG1 causes hypersuccinylation in leukemia cell lines, which impairs cell proliferation and leukemia progression. We hypothesize that increased histone H3 succinylation attenuates bromodomain interaction with chromatin, hence disrupting BRD4-mediated leukemogenic genes transcription. To confirm the hypothesis, we performed RNA-seq analysis in SUCLG1 knockout cell lines, JQ1-treated cells, Ksuc high and low primary AML patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE300338 | GEO | 2026/07/01

REPOSITORIES: GEO

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SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [ChIP-seq]

Project description:Succinyl-CoA synthetase was reported to sustain mitochondrial respiration and enhance leukemia proliferation in acute myeloid leukemia (AML). However, the biological mechanisms of mitochondrial metabolism and leukemia pathogenesis, beyond energy production, remains underexplored. Here we report that depletion of SUCLG1 causes hypersuccinylation in leukemia cell lines, which impairs cell proliferation and leukemia progression. We hypothesize that increased histone H3 succinylation attenuates bromodomain interaction with chromatin, hence disrupting BRD4-mediated leukemogenic genes transcription. To confirm the hypothesis, we performed ChIP-seq analysis on BRD4 in SUCLG1 knockout cell lines.

2026-07-21 | GSE272739 | GEO

SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [RNA-seq]

Project description:Succinyl-CoA synthetase was reported to sustain mitochondrial respiration and enhance leukemia proliferation. However, the biological mechanisms of mitochondrial metabolism and leukemia pathogenesis, beyond energy production, remains underexplored. Here we report that depletion of SUCLG1 causes hypersuccinylation in leukemia cell lines, which impairs cell proliferation and leukemia progression. We hypothesize that increased histone H3 succinylation attenuates bromodomain interaction with chromatin, hence disrupting BRD4-mediated leukemogenic genes transcription. To confirm the hypothesis, we performed RNA-seq analysis in SUCLG1 knockout cell lines, JQ1-treated cells, Ksuc high and low primary AML patients.

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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.

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

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SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [ChIP-seq]

Project description:SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [ChIP-seq]

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SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [RNA-seq]

Project description:SUCLG1-deficiency causes hypersuccinylation and impairs leukemia development [RNA-seq]

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Octanedioic-acid supplementation protects from acute kidney injury via stimulation of renal peroxisomal activity over mitochondrial

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2023-02-06 | MSV000091214 | MassIVE

Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation

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SIRT5 alleviate cardiomyocyte senescence in radiation-induced heart disease via desuccinylation of HADHB

Project description:<p>SIRT5 deficiency caused widespread protein hypersuccinylation in cardiac tissue. Succinylation proteomic analysis revealed HADHB as the key SIRT5 target, with lysine 292 (K292) being the dominant succinylation site. Functional studies demonstrated that K292 succinylation impairs HADHB-mediated fatty acid β-oxidation, ultimately promoting cardiomyocyte senescence. These findings reveal a critical regulatory axis involving SIRT5-HADHB succinylation in the pathogenesis of radiation-induced cardiomyopathy, providing new insights into potential therapeutic strategies.</p>

2026-03-15 | MTBLS14057 | MetaboLights

Sirtuin-5 is recruited to hepatic peroxisomes in mice fed dodecanedioic acid but has little impact on the peroxisomal succinylome

Project description:Lysine succinylation, and its reversal by sirtuin-5 (SIRT5), is known to modulate mitochondrial fatty acid beta-oxidation (FAO). We recently showed that feeding mice dodecanedioic acid, a 12-carbon dicarboxylic acid (DC12) that can be chain-shortened four rounds to succinyl-CoA, drives high-level protein hypersuccinylation in the peroxisome, particularly on peroxisomal FAO enzymes. But the ability of SIRT5 to reverse DC12-induced peroxisomal succinylation, or to regulate peroxisomal FAO in this context, remained unexplored. Here, we showed that feeding DC12 strongly recruits SIRT5 into hepatic peroxisomes. Knocking out SIRT5 impaired peroxisomal FAO as evidenced by reduced 14C-DC12 flux in liver homogenates and elevated levels of partially shortened DC12 catabolites in urine. Further, mass spectrometry revealed a trend toward less peroxisomal protein succinylation in SIRT5 knockout liver. This is consistent with reduced flux of DC12 through the peroxisomal FAO pathway, thereby reducing production of the succinyl-CoA that chemically reacts with lysine residues to produce protein succinylation. Mass spectrometry comparisons of site-level succinylation in wildtype and SIRT5 knockout liver did not reveal any clear pattern of SIRT5 target sites in the peroxisome after DC12 feeding. However, SIRT5 co-immunoprecipitated with 15 peroxisomal proteins including the key peroxisomal FAO enzymes acyl-CoA oxidase-1 and enoyl-CoA/3-hydroxyacyl-CoA dehydrogenase (EHHADH). In vitro, recombinant SIRT5 partially desuccinylated chemically modified recombinant ACOX1a, ACOX1b, and EHHADH. Desuccinylation by SIRT5 had no effect on enzyme activity for ACOX1a and EHHADH. For ACOX1b, SIRT5-mediated desuccinylation decreased activity by about 15%. Possible interpretations of this data are discussed.

2024-10-04 | MSV000096026 | MassIVE

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