HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239656 | GEO | 2024/01/16
REPOSITORIES: GEO
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Project description:Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. We report that HBO1 functions as a lysine lactyltransferase to regulate transcription. Quantitative proteomic analysis further revealsed 95 endogenous Kla sites targeted by HBO1, with the majority located on histones.
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Project description:Lactate produced in glycolysis has recently been discovered to modify lysine residues on eukaryotic proteins, a post-translational modification (PTM) called lysine lactylation (Kla). This modification not only participates in regulating gene expression through lactylation of histones, but also impacts the function of non-histone proteins. However, lactylation in prokaryotes has not been reported. Here, we report the identification of 1869 lysine lactylation sites in 465 proteins in the cariogenic organism Streptococcus mutans using a newly developed 4-dimensional label-free quantitative proteomic approach, representing the first Kla dataset in prokaryotes. Combining quantitative analysis, we report that the modification levels of 282 sites from 124 proteins increased by over 1.5-fold, and 80 sites from 52 proteins decreased by over 0.67-fold in the biofilm growth state. These results provide a systematic perspective of the distribution and function of Kla and improve our understanding of the role of lactate in the metabolic regulation of prokaryotes.
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Project description:Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.
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Project description:Lysine lactylation is a newly discovered post-translational modification (PTM) in histones and plays important roles in regulating gene expression. However, Kla in non-histone proteins in mammal is still unclear. Here, an analysis of lactylated proteins in gastric cancer AGS cells by using LC-MS/MS was conducted, and 2375 Kla sites on 1014 proteins were identified.
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Project description:Lysine lactylation (Kla) is a newly discovered posttranslational modification showing the addition of an L-lactate-derived lactyl group to the lysine residue. Histone lactylation has been found to regulate the downstream genes expression involved in the process of infection clearance, homeostasis retore, and tumorigenesis. Like other metabolite mediated PTMs, which the cellular levels of these metabolites affect the stoichiometry of the corresponding PTMs, the level of Kla also responds to the intracellular lactate concentration in a dose-dependent fashion associated with glycolysis metabolism. It has long been noted that manipulation of glycolysis metabolism could affect the tendon cell function, tendon homeostasis, and healing process of tendon.Nonetheless, the lactylation sites and regulations in tendinopathy remain unexplored.
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