Cover Story Current Issue
The pancreas is a mixed gland primarily composed of exocrine tissue, which secretes digestive enzymes into the digestive tract, and an endocrine component organized into small clusters known as islets of Langerhans, constituting approximately 1% of the pancreatic mass. Each adult islet contains an average of 1,500 cells, including beta-, alpha- and delta-cells, which produce and secrete insulin (INS), glucagon (GCG), and somatostatin (SST) respectively. The destruction of insulin-producing beta-cells or the defective insulin secretion give rise to type 1 and type 2 diabetes mellitus, respectively. These chronic metabolic disorders are characterized by the dysregulation of glucose homeostasis.
Current Issue
Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites
Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites
Objectives
Histone acetylation is an important epigenetic modification that regulates various biological processes and cell homeostasis. Acetyl-CoA, a hub molecule of metabolism, is the substrate for histone acetylation, thus linking metabolism with epigenetic regulation. However, still relatively little is known about the dynamics of histone acetylation and its dependence on metabolic processes, due to the lack of integrated methods that can capture site-specific histone acetylation and deacetylation reactions together with the dynamics of acetyl-CoA synthesis.
Methods
In this study, we present a novel proteo-metabo-flux approach that combines mass spectrometry-based metabolic flux analysis of acetyl-CoA and histone acetylation with computational modelling. We developed a mathematical model to describe metabolic label incorporation into acetyl-CoA and histone acetylation based on experimentally measured relative abundances.
Results
We demonstrate that our approach is able to determine acetyl-CoA synthesis dynamics and site-specific histone acetylation and deacetylation reaction rate constants, and that consideration of the metabolically labelled acetyl-CoA fraction is essential for accurate determination of histone acetylation dynamics. Furthermore, we show that without correction, changes in metabolic fluxes would be misinterpreted as changes in histone acetylation dynamics, whereas our proteo-metabo-flux approach allows to distinguish between the two processes.
Conclusions
Our proteo-metabo-flux approach expands the repertoire of metabolic flux analysis and cross-omics and represents a valuable approach to study the regulatory interplay between metabolism and epigenetic regulation by histone acetylation.
Articles in Press
Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites
Linking metabolism and histone acetylation dynamics by integrated metabolic flux analysis of Acetyl-CoA and histone acetylation sites
Objectives
Histone acetylation is an important epigenetic modification that regulates various biological processes and cell homeostasis. Acetyl-CoA, a hub molecule of metabolism, is the substrate for histone acetylation, thus linking metabolism with epigenetic regulation. However, still relatively little is known about the dynamics of histone acetylation and its dependence on metabolic processes, due to the lack of integrated methods that can capture site-specific histone acetylation and deacetylation reactions together with the dynamics of acetyl-CoA synthesis.
Methods
In this study, we present a novel proteo-metabo-flux approach that combines mass spectrometry-based metabolic flux analysis of acetyl-CoA and histone acetylation with computational modelling. We developed a mathematical model to describe metabolic label incorporation into acetyl-CoA and histone acetylation based on experimentally measured relative abundances.
Results
We demonstrate that our approach is able to determine acetyl-CoA synthesis dynamics and site-specific histone acetylation and deacetylation reaction rate constants, and that consideration of the metabolically labelled acetyl-CoA fraction is essential for accurate determination of histone acetylation dynamics. Furthermore, we show that without correction, changes in metabolic fluxes would be misinterpreted as changes in histone acetylation dynamics, whereas our proteo-metabo-flux approach allows to distinguish between the two processes.
Conclusions
Our proteo-metabo-flux approach expands the repertoire of metabolic flux analysis and cross-omics and represents a valuable approach to study the regulatory interplay between metabolism and epigenetic regulation by histone acetylation.
2022 impact factor: 6.6
You are what you eat
Here is a video of Vimeo. When the iframes is activated, a connection to Vimeo is established and, if necessary, cookies from Vimeo are also used. For further information on cookies policy click here.