Similar Datasets
Project description:Lysine succinylation (Ksucc) as an evolutionarily conserved and widespread post-translational modification has been identified. However, the mechanism of succinylation modulation remains unclear. Here, we report a histone acetyltransferase is a succinyltransferase, essentially enhancing the tumor growth and metastasis.
2020-12-10 | PXD013781 | Pride
Project description:Histone post-translational modifications (PTMs) are key players in chromatin regulation. The recent identification of novel histone acylations raised important questions regarding their role in transcriptional regulation. In this study, we characterized the role of succinylation of H3K122 (H3K122succ), located on the lateral surface of the histone octamer, in transcription and in chromatin function. Using chromatin, site-specifically succinylated at H3K122, we found that the presence of H3K122succ is sufficient to stimulate transcription in vitro. In line with this H3K122succ was enriched on promoters of active genes in mammalian cells and enrichment levels scale with gene expression. Furthermore, we show that the p300 and CBP co-activators are H3K122 succinyltransferases and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays we demonstrate a direct effect of H3K122succ on nucleosome stability indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the molecular mechanisms of H3K122succ in transcriptional regulation and they highlight a structural function for H3K122succ through direct perturbation of nucleosomes.
2021-02-01 | GSE152019 | GEO
Project description:Lysine succinylation is one of the major post-translational modifications occurred on histones and is believed to have significant roles in regulation of chromatin structure and function. Currently, histone desuccinylation is widely believed to be exerted by the members of SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, integrated analysis revealed that the promoter histone succinylation positively correlates with the transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation.
2023-07-03 | GSE234005 | GEO
Project description:Lysine succinylation is one of the major post-translational modifications occurred on histones and is believed to have significant roles in regulation of chromatin structure and function. Currently, histone desuccinylation is widely believed to be exerted by the members of SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, integrated analysis revealed that the promoter histone succinylation positively correlates with the transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation.
2023-07-03 | GSE234004 | GEO
Project description:We report the nuclear Gcn5/α-KGDH complex plays vital role in histone H3 K79 succinylation. By obtaining over 731 million reads from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of histone H3 K79 succinylation, Gcn5, and α-KGDH in U251 cells.
2017-12-13 | GSE97994 | GEO
Project description:We report the the effect of PGAM1 succinylation on gene expression profiling.
2020-01-01 | GSE131126 | GEO
Project description:The energetic costs of duplicating chromatin are large and therefore likely depend on nutrient sensing checkpoints and metabolic inputs. By studying chromatin modifiers regulated by epithelial growth factor, we identified histone acetyltransferase 1 (HAT1) as an induced gene that enhances proliferation through coordinating histone production, acetylation and glucose metabolism. In addition to its canonical role as a cytoplasmic histone H4 acetyltransferase, we isolated a HAT1-containing complex bound specifically at promoters of H4 genes. HAT1-dependent transcription of H4 genes required an acetate-sensitive promoter element. HAT1 expression was critical for S-phase progression and maintenance of H3 lysine 9 acetylation at proliferation-associated genes, including histone genes. Therefore, these data describe a feed-forward circuit whereby HAT1 captures acetyl-groups on nascent histones and drives H4 production by chromatin binding to support chromatin replication and acetylation. These findings have important implications for human disease, since high HAT1 levels associate with poor outcomes across multiple cancer types.
2019-07-02 | GSE117472 | GEO
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 | GSE208691 | GEO
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
Project description:We report that HAT1 regulates chromatin accessibility of large chromosomal domains.
2021-12-01 | GSE178590 | GEO