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Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.

ABSTRACT: The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences of RutR acetylation on the transcriptional level. We propose a model in which RutR acetylation follows different kinetic profiles either reacting non-enzymatically with acetyl-phosphate or enzymatically catalysed by the lysine acetyltransferases PatZ/YfiQ and YiaC. The NAD⁺-dependent sirtuin deacetylase CobB reverses enzymatic and non-enzymatic acetylation of RutR playing a dual regulatory and detoxifying role. By detecting cellular acetyl-CoA, NAD⁺ and acetyl-phosphate, bacteria apply lysine acetylation of transcriptional regulators to sense the cellular metabolic state directly adjusting gene expression to changing environmental conditions.

SUBMITTER: Kremer M

PROVIDER: S-EPMC10891134 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.

Kremer Magdalena M Schulze Sabrina S Eisenbruch Nadja N Nagel Felix F Vogt Robert R Berndt Leona L Dörre Babett B Palm Gottfried J GJ Hoppen Jens J Girbardt Britta B Albrecht Dirk D Sievers Susanne S Delcea Mihaela M Baumann Ulrich U Schnetz Karin K Lammers Michael M

Nature communications 20240223 1

The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences o ...[more]

PMID: 38395951

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Project description:Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality worldwide. lysine acetylation regulators (LARs) dynamically regulate Lysine acetylation modification which plays an important regulatory role in cancer. Therefore, we aimed to explore the potential clinical prognostic value of LARs in HCC. Methods: Differentially expressed LARs in normal liver and HCC tissues were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To identify genes with prognostic value and establish the risk characteristics of LARs, consensus clustering was employed. We used univariate Cox regression survival analysis and LASSO Cox regression based on LARs to determine the independent prognostic signature of HCC. CIBERSORT and Gene Set Enrichment Analysis (GSEA) were used to estimate immune infiltration and functional enrichment analysis respectively. The expression of LAR was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). statistical analyses were conducted using SPSS and R software. Results: In this study, the 33 LARs expression data and corresponding clinical information of HCC were obtained using TCGA and ICGC datasets. We found majority of the LARs were differentially expressed. Consensus cluster analysis was carried out based on the TCGA cohort, and three HCC subtypes (cluster 1, 2, and 3) were obtained. The LA3 subgroup had the worst clinical outcomes. Nine key LARs were identified to affect prognosis. The results showed that LARs signature has a strong independent prognostic value in HCC patients, whether in the training datasets or in the testing datasets. GSEA results showed that various tumor-related processes and pathways were abundant in the high-risk groups. RT-qPCR results showed that HAT1, HDAC1, HDAC2, HDAC4, and HDAC11 were highly expressed in HCC cells. Conclusion: Our results suggest that LARs play critical roles in HCC and are helpful for individual prognosis monitoring and clinical decision-making of HCC.

Dataset Information

Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.

Publications

Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.

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