Histone crotonylation promotes endoderm differentiation. [scRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130341 | GEO | 2021/02/23
REPOSITORIES: GEO
Similar Datasets
Project description:Protein acetylation and crotonylation are important post-translational modifications (PTMs) of lysine. In animal cells, histone lysines are crotonylated or acetylated depends on the relative intracellular concentrations of crotonyl-CoA and acetyl-CoA, and adding crotonate to cell cultures, or reducing the intracellular levels of acetyl-CoA, leads to an increase in histone crotonylation through the direct production of crotonyl-CoA. However, in plant the relationship of acetylation and crotonylation and the effect of the concentration of acetyl-CoA on protein crotonylation were not well known. Our previous study showed that PhACL silencing changed the content of acetyl CoA in petunia corollas. In this study, we performed a global crotonylation proteome analysis of petunia (Petunia hybrida) and found that protein crotonylation have close relationship with protein acetylation and the protein with more crotonylation sites often had more acetylation sites. Crotonylated proteins and acetylated proteins enriched in many common KEGG pathway. However, PhACL silencing resulted in different KEGG pathway enrichment of proteins with different level of crotonylated sites and acetylated sites. Cytoplasm non-histone lysine crotonylation may not depend on the concentrations of acetyl-CoA in petunia corollas. There was a positive correlation between crotonylome and acetylome expression levels in corollas of PhACL-silenced plants and control.
2022-10-12 | PXD023270 | Pride
Project description:We examined the genome-wide distribution of histone crotonylation and H3K27ac in human embryonic stem cells and induced endoderm cells, by obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA. When compared to H3K27ac, histone crotonylation was more enriched in metabolic genes and in promoters at pluripotent state, while H3k27ac was enriched in the enhancers of endoderm genes. After endoderm differentiation, histone crotonylation and H3K27ac were both enriched in endoderm genes. Moreover, the enrichment of histone crotonylation was more remarkable than that of H3K27ac. Our data indicate that histone crotonylation correlates with endoderm differentiation.
2021-02-23 | GSE130344 | GEO
Project description:Histone crotonylation promotes endoderm differentiation. [scRNA-Seq]
| PRJNA535524 | ENA
Project description:Lysine crotonylation on histones is a recently identified post-translational modification that has been demonstrated to associate with active promoters and to directly stimulate transcription.Given that crotonyl-CoA is essential for the acyl transfer reaction and it is a metabolic intermediate widely localized within the cell, we postulate that lysine crotonylation on non-histone proteins could also widely exist. Using specific antibody to enrich crotonylated lysine(Kcr) peptides followed by high-resolution mass spectrometry analysis reveals that crotonylated proteins and lysine residues. Bioinformatic analysis reveals that crotonylated proteins are particularly enriched in the nuclei, that lysine crotonylation alters level of the modified proteins in the chromatin and that cotonylation of a subset of proteins influences DNA replication and cell cycle. Taken together, our data indicate that lysine crotonylation could be induced in a large number of proteins other than histones and this type of acyl modification could play an important role regulating multiple cellular processes.
2016-06-11 | MSV000079810 | MassIVE
Project description:Chronic kidney disease (CKD) is characterized by sustained inflammation and progressive fibrosis, however therapies to slow CKD progression are limited. Histone lysine crotonylation (Kcr) as a novel post-translational modification is widespread as acetylation (Kac), but its roles in CKD are largely unknown. In the study, we firstly reported that the nuclear histone Kcr in tubular epithelial cells was significantly elevated in fibrotic kidney of patients and mice, which was positively correlated with the progression of disease. Interestingly, abnormal increase of histone 3 lysine 9 crotonylation (H3K9cr) in kidneys of unilateral ureteric obstruction (UUO) and folic acid nephropathy (FAN) was completely different to the stable expression of H3K9ac, indicating that H3K9cr may exert extraordinary functions in kidney fibrosis. By screening these crotonylated/acetylated factors, crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) remarkably promoted H3K9cr without influencing H3K9ac to trigger proinflammatory cytokine IL-1β transcription. Furthermore, genetic and pharmacologic inhibition of ACSS2 both attenuated kidney injury and fibrosis, as well as suppressed H3K9cr-mediated IL-1β expression, which thus to alleviate IL-1β-dependent macrophage activation and tubular cell senescence. Collectively, our finding uncovers that H3K9cr plays a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive target for strategies that aim to slow fibrotic kidney disease progression
2024-02-08 | GSE245390 | GEO
Project description:Chronic kidney disease (CKD) is characterized by sustained inflammation and progressive fibrosis, however therapies to slow CKD progression are limited. Histone lysine crotonylation (Kcr) as a novel post-translational modification is widespread as acetylation (Kac), but its roles in CKD are largely unknown. In the study, we firstly reported that the nuclear histone Kcr in tubular epithelial cells was significantly elevated in fibrotic kidney of patients and mice, which was positively correlated with the progression of disease. Interestingly, abnormal increase of histone 3 lysine 9 crotonylation (H3K9cr) in kidneys of unilateral ureteric obstruction (UUO) and folic acid nephropathy (FAN) was completely different to the stable expression of H3K9ac, indicating that H3K9cr may exert extraordinary functions in kidney fibrosis. By screening these crotonylated/acetylated factors, crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) remarkably promoted H3K9cr without influencing H3K9ac to trigger proinflammatory cytokine IL-1β transcription. Furthermore, genetic and pharmacologic inhibition of ACSS2 both attenuated kidney injury and fibrosis, as well as suppressed H3K9cr-mediated IL-1β expression, which thus to alleviate IL-1β-dependent macrophage activation and tubular cell senescence. Collectively, our finding uncovers that H3K9cr plays a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive target for strategies that aim to slow fibrotic kidney disease progression
2024-02-08 | GSE253032 | GEO
Project description:Lysine crotonylation (Kcr) is a recently-identified protein short-chain acylation. We have previously reported that chromodomain Y-like transcription corepressor CDYL acts as a crotonyl-CoA hydratase and negatively regulates histone Kcr. However, the global crotonylome of CDYL-regulated Kcr on non-histone substrates remains unclear. Using proteome-wide quantitative Kcr analysis, we identified 14,311 Kcr sites across 3,734 proteins in HeLa cells, providing by far the largest crotonylome data set from a single study. Upon depletion of CDYL, 1,141 Kcr sites from 759 proteins were increased by more than 1.5 fold, and 933 Kcr sites from 528 proteins were decreased by more than 0.67 fold. Upregulated crotonylome alterations upon CDYL depletion include components from diverse cellular pathways such as RNA splicing, DNA replication, and amino acid metabolism. Specifically, CDYL regulates K88 and K379 of crotonylation on RPA1, which affects its binding to other DNA repair factors including BLM, DNA2L, RAD50 and WRN. We showed evidence that CDYL-mediated RPA1 crotonylation is critical for the homologous recombination (HR) repair of camptothecin (CPT)-induced DNA damage. Together, our results provide a broad lysine crotonylome in response to CDYL and shed new light on the role of RPA1 Kcr in DNA repair, implicating functional importance of Kcr on non-histone substrates in diverse cellular processes.
2020-04-02 | PXD013616 | Pride
Project description:To gain a deeper insight into how histone lysine crotonylation regulates embryonic neural stem/progenitor cells (NSPCs) proliferation and differentiation, ChIP-seq and RNA-seq were performed to analyze the genome-wide changes of histone Kcr and transcriptiome changes stimulated with crotonate and MS-275 in E13.5 NSPCs.
2021-06-22 | GSE124540 | GEO
Project description:CurrentNeonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.
2022-09-27 | GSE205143 | GEO