Global profiling of crotonylation on non-histone proteins.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu W
PROVIDER: S-EPMC5518986 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Global profiling of crotonylation on non-histone proteins.
Xu Weizhi W Wan Junhu J Zhan Jun J Li Xueying X He Huiying H Shi Zhaomei Z Zhang Hongquan H
Cell research 20170421 7
Similar Datasets
Project description:Zebrafish embryos are translucent and develop rapidly in individual eggs ex utero; they are widely used as models for embryogenesis and organ development for human diseases and drug discovery. Lysine crotonylation (Kcr) is a type of histone post-translational modifications discovered in 2011. Kcr dynamics are involved in gene expression regulation and acute kidney injury; however, little is known about the effects of Kcr on non-histone proteins. In the present study, we conducted the first proteome-wide profiling of Kcr in zebrafish larvae and identified 557 Kcr sites on 218 proteins, representing the Kcr event in zebrafish. We identified two types of Kcr motifs containing hydrophobic (Leu, Ile, Val) and acidic (Asp and Glu) amino acids near the modified lysine residues. Our results show that both crotonylated proteins and sites of crotonylation were evolutionarily conserved between zebrafish embryos and humans. Specifically, Kcr on ribosomal proteins and myofilament proteins, including myosin, tropomyosin and troponin, were widely enriched. Interestingly, 55 lysine crotonylation sites on myosin were distributed throughout coiled coil regions. Therefore, Kcr may regulate muscle contraction and protein synthesis. Our results provide a foundation for future studies on the effects of lysine crotonylation on aging and heart failure.
| S-EPMC5827021 | biostudies-literature
Project description:Lysine crotonylation modification is a novel acylation modification that is similar to acetylation modification. Studies have found that protein acetylation plays an important regulatory part in the occurrence and prevention of obesity and is involved in the regulation of glucose metabolism, tricarboxylic acid cycle, white fat browning and fatty acid metabolism. Therefore, we speculate that protein crotonylation may also play a more vital role in regulating the browning of white fat. To verify this conjecture, we identified 7254 crotonyl modification sites and 1629 modified proteins in iWAT of white fat browning model mice by affinity enrichment and liquid chromatography-mass spectrometry (LC-MS/MS). We selected five representative proteins in the metabolic process, namely glycerol-3-phosphate dehydrogenase 1 (GPD1), fatty acid binding protein 4 (FABP4), adenylate kinase 2 (AK2), triosephosphate isomerase 1 (TPI1) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8). Through qPCR, Western blotting, immunofluorescence staining, Oil Red O staining and HE staining, we demonstrated that GPD1 and FABP4 inhibited white fat browning, while AK2, TPI1 and NDUFA8 promoted white fat browning. GPD1 and FABP4 proteins were downregulated by crotonylation modification, while AK2, TPI1 and NDUFA8 proteins were upregulated by crotonylation modification. Further detection found that the crotonylation modification of GPD1, FABP4, AK2, TPI1 and NDUFA8 promoted white fat browning, which was consistent with the sequencing results. These results indicate that the protein crotonylation is involved in regulating white fat browning, which is of great significance for controlling obesity and treating obesity-related diseases.
| S-EPMC9658748 | biostudies-literature
Project description:BackgroundLysine crotonylation (Kcr) is a crucial protein post-translational modification found in histone and non-histone proteins. It plays a pivotal role in regulating diverse biological processes in both animals and plants, including gene transcription and replication, cell metabolism and differentiation, as well as photosynthesis. Despite the significance of Kcr, detection of Kcr sites through biological experiments is often time-consuming, expensive, and only a fraction of crotonylated peptides can be identified. This reality highlights the need for efficient and rapid prediction of Kcr sites through computational methods. Currently, several machine learning models exist for predicting Kcr sites in humans, yet models tailored for plants are rare. Furthermore, no downloadable Kcr site predictors or datasets have been developed specifically for plants. To address this gap, it is imperative to integrate existing Kcr sites detected in plant experiments and establish a dedicated computational model for plants.ResultsMost plant Kcr sites are located on non-histones. In this study, we collected non-histone Kcr sites from five plants, including wheat, tabacum, rice, peanut, and papaya. We then conducted a comprehensive analysis of the amino acid distribution surrounding these sites. To develop a predictive model for plant non-histone Kcr sites, we combined a convolutional neural network (CNN), a bidirectional long short-term memory network (BiLSTM), and attention mechanism to build a deep learning model called PlantNh-Kcr. On both five-fold cross-validation and independent tests, PlantNh-Kcr outperformed multiple conventional machine learning models and other deep learning models. Furthermore, we conducted an analysis of species-specific effect on the PlantNh-Kcr model and found that a general model trained using data from multiple species outperforms species-specific models.ConclusionPlantNh-Kcr represents a valuable tool for predicting plant non-histone Kcr sites. We expect that this model will aid in addressing key challenges and tasks in the study of plant crotonylation sites.
| S-EPMC10870457 | biostudies-literature
Project description:Histone crotonylation is a newly identified epigenetic modification that has a pronounced ability to regulate gene expression. It belongs to an expanding group of short chain lysine acylations that also includes the extensively studied mark histone acetylation. Emerging evidence suggests that histone crotonylation is functionally distinct from histone acetylation and that competition for sites of modification, which reflects the cellular metabolic status, could be an important epigenetic mechanism that regulates diverse processes. Here, we discuss the enzymatic and metabolic regulation of histone crotonylation, the "reader" proteins that selectively recognise this modification and translate it into diverse functional outcomes within the cell, as well as the identified physiological roles of histone crotonylation, which range from signal-dependent gene activation to spermatogenesis and tissue injury.
| S-EPMC8055951 | biostudies-literature
Project description: Not available
| S-EPMC4856769 | biostudies-literature
Project description:In Brucella spp., the type IV secretion system (T4SS) is essential for bacterial intracellular survival and inhibition of the host innate immune response. The Brucella T4SS secretes 15 different effectors to escape host immunity and promote intracellular replication. Among them, BspF has a GNAT-family acetyltransferase domain, implying its acetyltransferase activity. We confirmed that BspF has acetyltransferase activity (data not shown) and de-crotonyltransferase activity. However, BspF overexpressed in HEK-293T cells can also enhance octamer crotonylation in vitro. Then we enriched crotonylated proteins and conducted LC-MS to study the crotonylation changes of proteins in HEK-293T cells caused by BspF overexpression. A total of 5,559 crotonylation sites were identified on 1,525 different proteins, of which 331 sites on 265 proteins were significantly changed. We found that Rab9A and RAP1B in proteomics data have a great impact on Brucella survival, so we speculate that BspF may influence the function of host proteins by altering crotonylation, thereby promoting the intracellular propagation of Brucella.
| S-EPMC7821425 | biostudies-literature
Project description:Histone post-translational modifications (PTMs), particularly lysine acetylation (Kac), are critical epigenetic regulators of gene transcription underlying long-term memory consolidation. Beyond Kac, several other non-acetyl acylations have been identified, but their role in memory consolidation remains unknown. Here, we demonstrate histone lysine crotonylation (Kcr) as a key molecular switch of hippocampal memory storage. Spatial memory training induces distinct spatiotemporal patterns of Kcr induction in the dorsal hippocampus of mice. Through genetic and pharmacological manipulations, we show that reducing hippocampal Kcr levels impairs long-term memory, while increasing Kcr enhances memory. Utilizing single-nuclei multiomics, we delineate that Kcr enhancement during memory consolidation activates transcription of genes involved in neurotransmission and synaptic function within hippocampal excitatory neurons. Cell-cell communication analysis further inferred that Kcr enhancement strengthens glutamatergic signaling within principal hippocampal neurons. Our findings establish Kcr as a novel epigenetic mechanism governing memory consolidation and provide a foundation for therapeutic strategies targeting memory-related disorders.
| S-EPMC11870504 | biostudies-literature
Project description: Not available
| S-EPMC6821229 | biostudies-literature
Project description:Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR through increased histone acetylation and reduced histone methylation. Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone crotonylation-induced HIV replication and reactivation. ACSS2 induction was highly synergistic in combination with either a protein kinase C agonist (PEP005) or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was significantly induced in intestinal mucosa in vivo, which correlated with altered fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication.
| S-EPMC5824862 | biostudies-literature