Changes in Acetyl CoA Levels during the Early Embryonic Development of Xenopus laevis

Tsuchiya, Yugo; Pham, Uyen; Hu, Wanzhou; Ohnuma, Shin-ichi; Gout, Ivan

doi:10.1371/journal.pone.0097693

Cited by 32 publications

(30 citation statements)

References 41 publications

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“…By further characterizing the selectivity changes of different KATs, we could better understand how to regulate their activity through means such as limiting acetyl-CoA concentrations. It is also possible that such a mechanism exists in vivo : it has recently been demonstrated that during early development, a cell undergoes changes to acetyl-CoA levels, which also correlate with changes to histone acetylation 10 . Based on our findings, it possible that these changes in acetyl-CoA could affect p300 selectivity, and correlate with changes in the histone acetylation pattern.…”

Section: Resultsmentioning

confidence: 99%

Changing the Selectivity of p300 by Acetyl-CoA Modulation of Histone Acetylation

et al. 2014

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Determining how histone acetylation is regulated is vital for treating the many diseases associated with its misregulation, including heart disease, neurological disorders, and cancer. We have previously reported that acetyl-CoA levels alter p300 histone acetylation in a site-specific manner in vitro. Here we further investigate how changing acetyl-CoA concentrations alter the histone acetylation pattern by altering p300 specificity. Interestingly, these changes are not a simple global change in acetylation, but rather site specific changes, whereby acetylation at some sites increase while others decrease. We also demonstrate how the p300 inhibitor C646 can pharmacologically alter p300 histone acetylation patterns in vitro and in cells. This study provides insight into the mechanisms regulating p300 residue specificity, a potential means for altering p300 dependent histone acetylation, and an investigation into altering histone acetylation patterns in cells.

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Section: Resultsmentioning

confidence: 99%

Changing the Selectivity of p300 by Acetyl-CoA Modulation of Histone Acetylation

et al. 2014

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“…Thus, acetyl-CoA levels have been shown to vary even in the course of embryonic development (Tsuchiya et al, 2014). Unfortunately, however, acetyl-CoA is generally quantified in whole-cell or whole-organ extracts, and very few studies have measured changing acetyl-CoA concentrations at the subcellular level.…”

Section: Fluctuations Of Acetyl-coa Levelsmentioning

confidence: 99%

Acetyl Coenzyme A: A Central Metabolite and Second Messenger

et al. 2015

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Acetyl-coenzyme A (acetyl-CoA) is a central metabolic intermediate. The abundance of acetyl-CoA in distinct subcellular compartments reflects the general energetic state of the cell. Moreover, acetyl-CoA concentrations influence the activity or specificity of multiple enzymes, either in an allosteric manner or by altering substrate availability. Finally, by influencing the acetylation profile of several proteins, including histones, acetyl-CoA controls key cellular processes, including energy metabolism, mitosis, and autophagy, both directly and via the epigenetic regulation of gene expression. Thus, acetyl-CoA determines the balance between cellular catabolism and anabolism by simultaneously operating as a metabolic intermediate and as a second messenger.

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“…Fasting or caloric restriction leads to a drop of acetyl-CoA levels in heart, muscle, and liver tissue (Hebert et al 2013;Mariño et al 2014). Acetyl-CoA levels have even been shown to vary during embryonic development and aging (Tsuchiya et al 2014;Peleg et al 2016). These observations raise the question of whether changes in acetyl-CoA levels may van der Knaap and Verrijzer have an impact on chromatin acetylation and transcription.…”

Section: The Interface Between Metabolism and Gene Expressionmentioning

confidence: 99%

Undercover: gene control by metabolites and metabolic enzymes

2016

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To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awareness that central components of intermediary metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such, their concentrations constitute a potential regulatory interface between the metabolic and chromatin states. In addition, there is increasing evidence for a direct involvement of classic metabolic enzymes in gene expression control. These dual-function proteins may provide a direct link between metabolic programing and the control of gene expression. Here, we discuss our current understanding of the molecular mechanisms connecting metabolism to gene expression and their implications for development and disease.Metabolism and gene regulation are two fundamental biological processes that are essential to all living organisms. Homeostasis, cell growth, and differentiation all require the coordination of metabolic state and gene expression programs. Nevertheless, how expression of the genome adapts to metabolic state or environmental changes is not well understood. One level of regulation involves signal transduction pathways that control key transcription factors that act as master regulators of gene expression programs. In addition, post-translational modifications (PTMs) of chromatin play a major role in the activation or repression of gene transcription. These include acetylation, methylation, and phosphorylation of the histones and DNA methylation. Some of these chromatin modifications are involved in the maintenance of stable patterns of gene expression, usually referred to as epigenetic regulation. Pertinently, the activity of enzymes that modulate chromatin is critically dependent on central metabolites as cofactors or cosubstrates. Thus, the availability of metabolites that are required for the activity of histone-modifying enzymes may connect metabolism to chromatin structure and gene expression. Finally, selective metabolic enzymes act in the nucleus to adjust gene transcription in response to changes in metabolic state. Here, we review the interface between metabolism and gene transcription. We focus on the molecular mechanisms involved and discuss unresolved issues and implications for development and disease. The basics of metabolism and gene expression controlMetabolism is the total of all chemical reactions in cells and organisms that maintain life. Metabolism can be divided into two classes: catabolic processes (the breakdown of molecules that usually results in the release of energy) and anabolic processes (the synthesis of components such as proteins, lipids, and nucleic acids, which costs energy). Cellular (or intermediary) metabolism is organized in separate chemical pathways formed by a chain of linked enzymatic reactions in wh...

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Changes in Acetyl CoA Levels during the Early Embryonic Development of Xenopus laevis

Cited by 32 publications

References 41 publications

Changing the Selectivity of p300 by Acetyl-CoA Modulation of Histone Acetylation

Changing the Selectivity of p300 by Acetyl-CoA Modulation of Histone Acetylation

Acetyl Coenzyme A: A Central Metabolite and Second Messenger

Undercover: gene control by metabolites and metabolic enzymes

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