H3K4 Methylation in Aging and Metabolism
Open Access
- 18 June 2021
- journal article
- review article
- Published by MDPI AG in Epigenomes
- Vol. 5 (2), 14
- https://doi.org/10.3390/epigenomes5020014
Abstract
During the process of aging, extensive epigenetic alterations are made in response to both exogenous and endogenous stimuli. Here, we summarize the current state of knowledge regarding one such alteration, H3K4 methylation (H3K4me), as it relates to aging in different species. We especially highlight emerging evidence that links this modification with metabolic pathways, which may provide a mechanistic link to explain its role in aging. H3K4me is a widely recognized marker of active transcription, and it appears to play an evolutionarily conserved role in determining organism longevity, though its influence is context specific and requires further clarification. Interestingly, the modulation of H3K4me dynamics may occur as a result of nutritional status, such as methionine restriction. Methionine status appears to influence H3K4me via changes in the level of S-adenosyl methionine (SAM, the universal methyl donor) or the regulation of H3K4-modifying enzyme activities. Since methionine restriction is widely known to extend lifespan, the mechanistic link between methionine metabolic flux, the sensing of methionine concentrations and H3K4me status may provide a cogent explanation for several seemingly disparate observations in aging organisms, including age-dependent H3K4me dynamics, gene expression changes, and physiological aberrations. These connections are not yet entirely understood, especially at a molecular level, and will require further elucidation. To conclude, we discuss some potential H3K4me-mediated molecular mechanisms that may link metabolic status to the aging process.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST109-2320-B-001-017 -MY3)
- Academia Sinica, Taiwan (AS-108-TP-L07)
This publication has 174 references indexed in Scilit:
- Kinetochores Coordinate Pericentromeric Cohesion and Early DNA Replication by Cdc7-Dbf4 Kinase RecruitmentMolecular Cell, 2013
- The Hallmarks of AgingCell, 2013
- Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine MetabolismCell, 2013
- Forkhead Transcription Factors Establish Origin Timing and Long-Range Clustering in S. cerevisiaeCell, 2012
- DrosophilaSet1 is the major histone H3 lysine 4 trimethyltransferase with role in transcriptionThe EMBO Journal, 2011
- Histone Demethylase LSD1 Is a Folate-Binding ProteinBiochemistry, 2011
- Histone Methyl Transferases and Demethylases; Can They Link Metabolism and Transcription?Cell Metabolism, 2010
- A C. elegans LSD1 Demethylase Contributes to Germline Immortality by Reprogramming Epigenetic MemoryCell, 2009
- Methylation of Lysine 4 on Histone H3: Intricacy of Writing and Reading a Single Epigenetic MarkMolecular Cell, 2007
- Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1Cell, 2004