Dataset Information

C?-Pathways in Methyloversatilis universalis FAM5: Genome Wide Gene Expression and Mutagenesis Studies.

ABSTRACT: Methyloversatilis universalis FAM5 utilizes single carbon compounds such as methanol or methylamine as a sole source of carbon and energy. Expression profiling reveals distinct sets of genes altered during growth on methylamine vs methanol. As expected, all genes for the N-methylglutamate pathway were induced during growth on methylamine. Among other functions responding to the aminated source of C?-carbon, are a heme-containing amine dehydrogenase (Qhp), a distant homologue of formaldehyde activating enzyme (Fae3), molybdenum-containing formate dehydrogenase, ferredoxin reductase, a set of homologues to urea/ammonium transporters and amino-acid permeases. Mutants lacking one of the functional subunits of the amine dehydrogenase (?qhpA) or ?fae3 showed no growth defect on C?-compounds. M. universalis FAM5 strains with a lesion in the H?-folate pathway were not able to use any C?-compound, methanol or methylamine. Genes essential for C?-assimilation (the serine cycle and glyoxylate shunt) and H?MTP-pathway for formaldehyde oxidation showed similar levels of expression on both C?-carbon sources. M. universalis FAM5 possesses three homologs of the formaldehyde activating enzyme, a key enzyme of the H?MTP-pathway. Strains lacking the canonical Fae (fae1) lost the ability to grow on both C?-compounds. However, upon incubation on methylamine the fae1-mutant produced revertants (?fae1(R)), which regained the ability to grow on methylamine. Double and triple mutants (?fae1(R)?fae3, or ?fae1(R)?fae2 or ?fae1(R)?fae2?fae3) constructed in the revertant strain background showed growth similar to the ?fae1(R) phenotype. The metabolic pathways for utilization of methanol and methylamine in Methyloversatilis universalis FAM5 are reconstructed based on these gene expression and phenotypic data.

SUBMITTER: Good NM

PROVIDER: S-EPMC5023235 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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C₁-Pathways in Methyloversatilis universalis FAM5: Genome Wide Gene Expression and Mutagenesis Studies.

Good Nathan M NM Lamb Andrew A Beck David A C DA Martinez-Gomez N Cecilia NC Kalyuzhnaya Marina G MG

Microorganisms 20150409 2

Methyloversatilis universalis FAM5 utilizes single carbon compounds such as methanol or methylamine as a sole source of carbon and energy. Expression profiling reveals distinct sets of genes altered during growth on methylamine vs methanol. As expected, all genes for the N-methylglutamate pathway were induced during growth on methylamine. Among other functions responding to the aminated source of C₁-carbon, are a heme-containing amine dehydrogenase (Qhp), a distant homologue of formaldehyde acti ...[more]

PMID: 27682085

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Project description:Methyloversatilis universalis FAM5 utilizes single carbon compounds such as methanol or methylated amines as a sole source of carbon and energy. Expression profiling reveals distinct sets of genes altered during growth on methanol vs methylamine. Growth on methanol results in activation of mdh2 and a number of known accessory proteins. As expected, all genes for N-methylglutamate pathway were induced during growth on methylated amine. Among other functions, responding to a switch from methanol to methylated amines, are a heme-containing amine dehydrogenase (QHNDH), a PQQ-dependent methanol dehydrogenase homologue, a distant homologue of formaldehyde activating enzyme (fae3), molybdenum containing formate dehydrogenase, a set of transporters homologues to urea/ammonium transporters and amino-acid permeases. Genes encoding the PQQ-dependent methanol dehydrogenase and associated cytochrome, the enzymes from the assimilatory H4F-dependent pathway, and the tungsten-containing aldehyde oxidoreductase were down-regulated during growth on methylamine. Genes essential for carbon assimilation (serine cycle) and H4MTP-pathway for formaldehyde oxidation show similar level of expression on both C1-carbon sources. Phenotypic analysis of mutants lacking functional QHNDH had no growth defect on C1-compounds. M. universalis FAM5 strain with the methylene-tetrahydrofolate dehydrogenase lesion, a key enzyme of the H4-folate pathway, were not able to use any C1-compound, methanol or methylated amines. Methyloversatilis universalis FAM5 possesses three homologs of the formaldehyde activating enzymes. The relative expression of two of the formaldehyde activating enzyme (fae1) and fae2 did not change after the shift from methanol to methylamine growth. The relative expression of the third homologs, fae3, was significantly upregulated by methylamine. Single and double fae 2 and fae 3 mutants display similar to wild type growth on methanol or methylamine. Strains lacking fae1 lost the ability to grow on both C1-compounds. However upon incubation on methylated amines the fae1-mutant produce revertants (fae1R ). The revertant strains displayed an impaired growth on methylamine but were not able to use methanol. Double mutations in fae1R / fae3 or fae1R/fae2 and triple mutant fae1R/fae2/fae3 showed similar to fae1R phenotype. The metabolic pathways for utilization methanol and methylamine in Methyloversatilis universalis FAM5 are reconstructed.

Project description:Methyloversatilis universalis FAM5 utilizes single carbon compounds such as methanol or methylated amines as a sole source of carbon and energy. Expression profiling reveals distinct sets of genes altered during growth on methanol vs methylamine. Growth on methanol results in activation of mdh2 and a number of known accessory proteins. As expected, all genes for N-methylglutamate pathway were induced during growth on methylated amine. Among other functions, responding to a switch from methanol to methylated amines, are a heme-containing amine dehydrogenase (QHNDH), a PQQ-dependent methanol dehydrogenase homologue, a distant homologue of formaldehyde activating enzyme (fae3), molybdenum containing formate dehydrogenase, a set of transporters homologues to urea/ammonium transporters and amino-acid permeases. Genes encoding the PQQ-dependent methanol dehydrogenase and associated cytochrome, the enzymes from the assimilatory H4F-dependent pathway, and the tungsten-containing aldehyde oxidoreductase were down-regulated during growth on methylamine. Genes essential for carbon assimilation (serine cycle) and H4MTP-pathway for formaldehyde oxidation show similar level of expression on both C1-carbon sources. Phenotypic analysis of mutants lacking functional QHNDH had no growth defect on C1-compounds. M. universalis FAM5 strain with the methylene-tetrahydrofolate dehydrogenase lesion, a key enzyme of the H4-folate pathway, were not able to use any C1-compound, methanol or methylated amines. Methyloversatilis universalis FAM5 possesses three homologs of the formaldehyde activating enzymes. The relative expression of two of the formaldehyde activating enzyme (fae1) and fae2 did not change after the shift from methanol to methylamine growth. The relative expression of the third homologs, fae3, was significantly upregulated by methylamine. Single and double fae 2 and fae 3 mutants display similar to wild type growth M-BM- on methanol or methylamine. Strains lacking fae1 lost the ability to grow on both C1-compounds. However upon incubation on methylated amines the fae1-mutant produce revertants (fae1R ). The revertant strains displayed an impaired growth on methylamine but were not able to use methanol. Double mutations in fae1RM-BM- / fae3 or fae1R/fae2 and triple mutant fae1R/fae2/fae3 showed similar to fae1R phenotype. The metabolic pathways for utilization methanol and methylamine in Methyloversatilis universalis FAM5 are reconstructed. Methyloversatilis universalis FAM5 grown on methanol and methylamine with two biologial replicates for each condition. RNA-Seq was used for transcriptomics.

Project description:Osteoarthritis (OA) is the most common degenerative joint disorder worldwide. To identify more genetic signals, genome-wide association study (GWAS) has been widely used and elucidated some OA susceptibility genes. However, these susceptibility genes could only explain only a small part of heritability of OA. It is suggested that the identification of disease-related pathways may contribute to understand the genomic etiology of OA. Here, we integrated the GWAS into pathway analysis to identify novel OA risk pathways. In this study, we first selected 187 independent genetic variants identified by GWAS (P < 1.00E-05) and found that most of these genetic variants are noncoding mutations. We then conducted an expression quantitative trait loci analysis and found that 165 of these 187 genetic variants could significantly regulate the expression of nearby genes. Third, we identified OA susceptibility genes corresponding to these genetic variants, conducted a pathway analysis, and identified novel OA-related KEGG pathways, GO biological processes, GO molecular functions, and GO cellular components. In KEGG database, transforming growth factor β signaling pathway is the most significant signal (P = 5.98E-05) and is the only pathway after the BH multiple-test adjustment with false discovery rate (FDR) = 0.02. In GO database, we identified 24 statistically significant GO biological processes, one statistically significant GO molecular function, and five statistically significant GO cellular components (FDR < 0.05). These signals are related with chondrocyte differentiation and development, which are all known biological pathways associated with OA. Finally, we conducted an OA case-control gene expression analysis to evaluate the differential expression of these OA risk genes. Using an OA case-control gene expression analysis, we showed that 44 risk genes were suggestively differentially expressed in OA cases compared with controls (P < 0.05). Three genes, WWP2, COG5, and MAPT, were statistically differentially expressed in OA cases compared with controls (P < 0.05/122 = 4.10E-04). Hence, our findings may contribute to understanding the genomic etiology of OA.

Project description:Numerous genome-wide gene expression studies of bipolar disorder (BP) have been carried out. These studies are heterogeneous, underpowered and use overlapping samples. We conducted a systematic review of these studies to synthesize the current findings.We identified all genome-wide gene expression studies on BP in humans. We then carried out a quantitative mega-analysis of studies done with post-mortem brain tissue. We obtained raw data from each study and used standardized procedures to process and analyze the data. We then combined the data and conducted three separate mega-analyses on samples from 1) any region of the brain (9 studies); 2) the prefrontal cortex (PFC) (6 studies); and 3) the hippocampus (2 studies). To minimize heterogeneity across studies, we focused primarily on the most numerous, recent and comprehensive studies.A total of 30 genome-wide gene expression studies of BP done with blood or brain tissue were identified. We included 10 studies with data on 211 microarrays on 57 unique BP cases and 229 microarrays on 60 unique controls in the quantitative mega-analysis. A total of 382 genes were identified as significantly differentially expressed by the three analyses. Eleven genes survived correction for multiple testing with a q-value < 0.05 in the PFC. Among these were FKBP5 and WFS1, which have been previously implicated in mood disorders. Pathway analyses suggested a role for metallothionein proteins, MAP Kinase phosphotases, and neuropeptides.We provided an up-to-date summary of results from gene expression studies of the brain in BP. Our analyses focused on the highest quality data available and provided results by brain region so that similarities and differences can be examined relative to disease status. The results are available for closer inspection on-line at Metamoodics [http://metamoodics.igm.jhmi.edu/], where investigators can look up any genes of interest and view the current results in their genomic context and in relation to leading findings from other genomic experiments in bipolar disorder.

Dataset Information

C?-Pathways in Methyloversatilis universalis FAM5: Genome Wide Gene Expression and Mutagenesis Studies.

Publications

C₁-Pathways in Methyloversatilis universalis FAM5: Genome Wide Gene Expression and Mutagenesis Studies.

Similar Datasets

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