scholarly journals Trans-omic analysis reveals allosteric and gene regulation-axes for altered glucose-responsive liver metabolism associated with obesity

2019 ◽  
Author(s):  
Toshiya Kokaji ◽  
Atsushi Hatano ◽  
Yuki Ito ◽  
Katsuyuki Yugi ◽  
Miki Eto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Liver Metabolism ◽  
Metabolic Enzyme ◽  
Obese Mice ◽  
Glucose Administration ◽  
Healthy State ◽  
Rapid Changes ◽  
Metabolic Reactions ◽  
Allosteric Regulators

AbstractImpaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in the healthy and obese states, we constructed and analyzed trans-omic glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multi-omic time-course data from wild-type (WT) and leptin-deficient obese (ob/ob) mice after orally administered glucose. In WT mice, metabolic reactions were rapidly regulated (within 10 minutes of oral glucose administration) primarily by glucose-responsive metabolites, especially ATP and NADP+, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-dependent glucose-responsive genes encoding metabolic enzymes. Inob/obmice, most rapid regulation by glucose-responsive metabolites was absent; instead, glucose administration produced slow changes in the expression of metabolic enzyme-encoding genes to alter metabolic reactions in a time scale of hours. Few common regulatory events occurred in both the healthy and obese mice. Thus, our trans-omic network analysis revealed regulation of liver metabolism in response to glucose is mediated through different mechanisms in the healthy and obese states: Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, and slow transcriptional regulation dominates the obese state.One Sentence SummaryRapid changes in regulatory metabolites and gene expression dominate the healthy state, and slow transcriptional regulation dominates the obese state.

Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity

2020 ◽  
Vol 13 (660) ◽  
pp. eaaz1236
Author(s):  
Toshiya Kokaji ◽  
Atsushi Hatano ◽  
Yuki Ito ◽  
Katsuyuki Yugi ◽  
Miki Eto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Enzymes ◽  
Liver Metabolism ◽  
Metabolic Enzyme ◽  
Oral Glucose ◽  
Obese Mice ◽  
Wild Type ◽  
Glucose Administration ◽  
Metabolic Reactions ◽  
Allosteric Regulators

Impaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in healthy and obese states, we constructed and analyzed transomics glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multiomics time course data from wild-type and leptin-deficient obese (ob/ob) mice after orally administered glucose. In wild-type mice, metabolic reactions were rapidly regulated within 10 min of oral glucose administration by glucose-responsive metabolites, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-induced changes in the expression of glucose-responsive genes encoding metabolic enzymes. In ob/ob mice, the majority of rapid regulation by glucose-responsive metabolites was absent. Instead, glucose administration produced slow changes in the expression of carbohydrate, lipid, and amino acid metabolic enzyme–encoding genes to alter metabolic reactions on a time scale of hours. Few regulatory events occurred in both healthy and obese mice. Thus, our transomics network analysis revealed that regulation of glucose-responsive liver metabolism is mediated through different mechanisms in healthy and obese states. Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, whereas slow changes in gene expression dominate the obese state.

Interplay between Pur α and Egr-1 in the transcriptional regulation of amyloid precursor protein gene expression

2010 ◽  
Vol 34 (8) ◽  
pp. S27-S27
Author(s):  
Jianqi Cui ◽  
Xiuying Pei ◽  
Qian Zhang ◽  
Bassel E. Sawaya ◽  
Xiaohong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene

scholarly journals The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
José L Ruiz ◽  
Lisa C Ranford-Cartwright ◽  
Elena Gómez-Díaz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Anopheles Gambiae ◽  
Mosquito Control ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Malaria Vectors ◽  
Specific Gene ◽  
Mosquito Vector ◽  
Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

scholarly journals Interaction of 7SK with the Smn complex modulates snRNP production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Changhe Ji ◽  
Jakob Bader ◽  
Pradhipa Ramanathan ◽  
Luisa Hennlein ◽  
Felix Meissner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Fine Tuning ◽  
Global Changes ◽  
Functional Association ◽  
Transcriptional Inhibition ◽  
Smn Complex ◽  
Core Components

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

scholarly journals Fast and Efficient 5′P Degradome Library Preparation for Analysis of Co-Translational Decay in Arabidopsis

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 466
Author(s):  
Marie-Christine Carpentier ◽  
Cécile Bousquet-Antonelli ◽  
Rémy Merret
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Transcriptional Regulation ◽  
High Throughput ◽  
Library Preparation ◽  
Working Day ◽  
Set Up ◽  
Post Transcriptional Regulation ◽  
Commercial Kit

The recent development of high-throughput technologies based on RNA sequencing has allowed a better description of the role of post-transcriptional regulation in gene expression. In particular, the development of degradome approaches based on the capture of 5′monophosphate decay intermediates allows the discovery of a new decay pathway called co-translational mRNA decay. Thanks to these approaches, ribosome dynamics could now be revealed by analysis of 5′P reads accumulation. However, library preparation could be difficult to set-up for non-specialists. Here, we present a fast and efficient 5′P degradome library preparation for Arabidopsis samples. Our protocol was designed without commercial kit and gel purification and can be easily done in one working day. We demonstrated the robustness and the reproducibility of our protocol. Finally, we present the bioinformatic reads-outs necessary to assess library quality control.

Leuconostoc pseudomesenteroides improves microbiota dysbiosis and liver metabolism imbalance and ameliorates the correlation between dihydroceramide and strains of Firmicutes and Proteobacteria in high fat diet obese mice

2020 ◽  
Vol 11 (8) ◽  
pp. 6855-6865
Author(s):  
Mengzhen Sun ◽  
Qiya Wang ◽  
Maomao Zhang ◽  
Guohua Zhang ◽  
Tao Wu ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
High Fat Diet ◽  
Liver Metabolism ◽  
Fermented Foods ◽  
Obese Mice ◽  
High Fat ◽  
Leuconostoc Pseudomesenteroides

Leuconostoc pseudomesenteroides is widely isolated from fermented foods; however, the underlying molecular mechanism behind its anti-obesity function has rarely been studied.

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