Original Article
One-carbon metabolism and epigenetics: understanding the specificity
Samantha J. Mentch,
Jason W. Locasale,
Samantha J. Mentch
Field of Biochemistry, Molecular, and Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York
Search for more papers by this authorCorresponding Author
Jason W. Locasale
Field of Biochemistry, Molecular, and Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina
Duke Cancer Institute, Duke University Medical School, Durham, North Carolina
Duke Molecular Physiology Institute, Duke University Medical School, Durham, North Carolina
Address for correspondence: Jason W. Locasale, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C270A, Box 3813, Durham, NC 27710. [email protected]Search for more papers by this authorSamantha J. Mentch,
Jason W. Locasale,
Samantha J. Mentch
Field of Biochemistry, Molecular, and Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York
Search for more papers by this authorCorresponding Author
Jason W. Locasale
Field of Biochemistry, Molecular, and Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina
Duke Cancer Institute, Duke University Medical School, Durham, North Carolina
Duke Molecular Physiology Institute, Duke University Medical School, Durham, North Carolina
Address for correspondence: Jason W. Locasale, Department of Pharmacology and Cancer Biology, Duke University School of Medicine, LSRC C270A, Box 3813, Durham, NC 27710. [email protected]Search for more papers by this authorAbstract
One-carbon metabolism is a metabolic network that integrates nutrient status from the environment to yield multiple biological functions. The folate and methionine cycles generate S-adenosylmethionine (SAM), which is the universal methyl donor for methylation reactions, including histone and DNA methylation. Histone methylation is a crucial part of the epigenetic code and plays diverse roles in the establishment of chromatin states that mediate the regulation of gene expression. The activities of histone methyltransferases (HMTs) are dependent on intracellular levels of SAM, which fluctuate based on cellular nutrient availability, providing a link between cell metabolism and histone methylation. Here we discuss the biochemical properties of HMTs, their role in gene regulation, and the connection to cellular metabolism. Our emphasis is on understanding the specificity of this intriguing link.
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