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Published on: December 18, 2017
Moonlighting Enzymes at the Interface Between Metabolism and Epigenetics.
Jan A van der Knaap1, C Peter Verrijzer1
1Department of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands;
Metabolism and gene regulation are intricately linked, with metabolites influencing chromatin and gene expression. This bidirectional relationship, including metabolic enzymes directly impacting transcription, is often disrupted in cancer.
Area of Science:
- Molecular Biology
- Biochemistry
- Epigenetics
Background:
- Metabolism and gene regulation are essential for cellular homeostasis, growth, and development.
- Recent studies highlight a complex interplay between metabolic processes and gene expression control.
- Key metabolites can directly influence chromatin structure and gene activity by acting as cofactors for modifying enzymes.
Purpose of the Study:
- To discuss the bidirectional relationship between metabolism and chromatin.
- To explore how metabolic changes affect gene expression and vice versa.
- To examine the role of this interface in cancer biology.
Main Methods:
- Literature review and synthesis of current research findings.
- Analysis of the roles of metabolites in chromatin modification.
- Investigation of metabolic enzymes with direct roles in gene regulation.
- Examination of chromatin's intrinsic metabolic functions.
Main Results:
- Metabolites serve as substrates/cofactors for chromatin-modifying enzymes, thereby regulating gene expression.
- Certain metabolic enzymes possess 'moonlighting' functions, directly regulating transcription independently of their enzymatic activity.
- Chromatin itself exhibits metabolic functions beyond transcriptional regulation.
- The interplay between metabolism and chromatin is frequently altered in cancer cells.
Conclusions:
- A dynamic, bidirectional crosstalk exists between cellular metabolism and chromatin regulation.
- This metabolic-chromatin axis is crucial for normal cellular functions and is a significant factor in oncogenesis.
- Understanding this interface offers potential therapeutic targets for cancer treatment.
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