HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000492 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25470119_1.fastq.gz | Fastqsanger.gz | |||
| SRR25470119_2.fastq.gz | Fastqsanger.gz | |||
| SRR25470120_1.fastq.gz | Fastqsanger.gz | |||
| SRR25470120_2.fastq.gz | Fastqsanger.gz | |||
| SRR25470121_1.fastq.gz | Fastqsanger.gz |
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Project description:Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. Interestingly, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on TSSs and the regulated Kla can facilitate in signaling pathways and progress of tumorigenesis. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.
2024-01-16 | GSE239656 | GEO
Project description:Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a “writer” of Kbz in mammalian cells. In addition, we report the first benzoylome in mammalian cells, identifying 1747 Kbz sites, among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify key regulatory elements of the Kbz pathway, and reveal new enzymatic activity and functions of HBO1 in cellular physiology.
2022-10-14 | PXD034187 | Pride
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.
2024-04-13 | PXD051415 | Pride
Project description:Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently-identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNseq ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveal a vital role of histone Kla triggered by hypoxia in cancer.
2024-05-22 | GSE255352 | GEO
Project description:As a novel post-translational modification of histone derived from lactate, lysine lactylation (Kla) links lactate metabolism to epigenetic regulation, playing a role in modulation of gene expression in tumor and immune microenvironment. Evidence so far indicates that HDAC1-3 can catalyze the removal of Kla. However, the regulated targets of HDACs for Kla and functional consequence remain elusive. Herein, we used an antibody-based proximity labeling approach to identify SIRT3 binding to histone H3K9la and catalytic removal of the lactylationoup. The molecular docking results further revealed the mechanism of the binding of Kla peptide to SIRT3. More importantly, SIRT3 can specifically modulate the gene transcription by regulating H3K9la, inhibiting the progression of esophageal cancer cells (ESCC). In conclusion, our work identifies the delactylase of H3K9la and reveal an H3K9la-mediated molecular mechanism catalyzed by SIRT3 for gene transcription regulation in ESCC, and our findings provide an opportunity to investigate the physiological significance of Kla and shed light on the unknown cellular mechanisms controlled by SIRT3.
2024-08-18 | GSE274648 | GEO
Project description:Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a "writer" of Kbz in mammalian cells. In addition, we report the benzoylome in mammalian cells, identifying 1747 Kbz sites; among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify the regulatory elements of the Kbz pathway and reveal the non-canonical enzymatic activity and functions of HBO1 in cellular physiology.
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Project description:SMYD5 catalyzes histone H3 lysine 36 trimethylation at promoters
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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.
2023-08-24 | PXD037027 | Pride
Project description:Protein lactylation is a newly discovered posttranslational modification (PTM) and involved in multiple biological processes both in mammalian cells and rice grains. However, the function of lysine lactylation remains unexplored in wheat. In this study, we performed the first comparative proteomes and lysine lactylomes during seed germination of wheat. In total, 8,000 proteins and 927 lactylated sites in 394 proteins were identified at 0 and 12 hour after imbibition (HAI). Functional enrichment analysis showed that glycolysis and the TCA cycle related proteins were significantly enriched, and more differentially lactylated proteins were enriched in up-regulated lactylated proteins at 12 HAI vs 0 HAI through KEGG pathway and protein domain enrichment analysis compared to down-regulated lactylated proteins. Meanwhile, ten particularly preferred amino acids near lactylation sites were found in the embryos of germinated seeds: AA*KlaT, A***KlaD********A, KlaA**T****K, K******A*Kla, K*Kla********K, KlaA******A, Kla*A, KD****Kla, K********Kla and KlaG. These results supplied a comprehensive profile of lysine lactylation of wheat and indicated that protein lysine lactylation played important functions in several biological processes.
2024-01-26 | PXD046488 | Pride
Project description:KAT7 (HBO1) is a histone acetyltransferase required for histone H3 lysine 14 acetylation (H3K14ac) and normal levels of gene expression in hematopoietic stem and progenitor cells (HSPCs). The loss of H3K14ac was detected by western blot in whole bone marrow and by flow cytometry in specific HSPC populations. In order to determine the normal distribution of H3K14ac in the HSPC population a CUT&Tag experiment was performed using lineage negative, cKit positive Sca1 positive cells (LSK) and lineage negative, cKit positive Sca1 negative cells (progenitor cells). HBO1 was deleted using the poly(I:C) inducible MX1-cre recombinase transgene and compared to Kat7 heterozygous control cells, in which the MX1-cre was likewise induced. Analysis was performed at a stage when H3K14ac was no longer detectable by western blot. In order to control for the effects of PCR amplification and normalisation of library size before sequencing, equal numbers of Drosophila Schneider 2 cells were added to each sorted mouse cell population (“spike in”). After sequencing-read quality control, reads were mapped to a combined Mus musculus (Mm10) and Drosophila melanogaster (DmelR635) genome. To each mouse sample a normalisation factor based on the recovery of Drosophila reads within the same sample was applied. Genomic distribution of KAT7 (HBO1) was determined in control progenitor cells by CUT&Tag.
2021-10-13 | GSE185820 | GEO