PUBLICATION
The DNA methyltransferase DNMT3A contributes to autophagy long-term memory
- Authors
- González-Rodríguez, P., Cheray, M., Füllgrabe, J., Salli, M., Engskog-Vlachos, P., Keane, L., Cunha, V., Lupa, A., Li, W., Ma, Q., Dreij, K., Rosenfeld, M.G., Joseph, B.
- ID
- ZDB-PUB-200904-6
- Date
- 2020
- Source
- Autophagy 17(5): 1259-1277 (Journal)
- Registered Authors
- Keywords
- Autophagy, DNA methylation, MAP1LC3, epigenetics, transcription
- MeSH Terms
-
- DNA Methyltransferase 3A/metabolism*
- Methyltransferases/metabolism
- Autophagy/physiology*
- Humans
- Zebrafish/genetics
- Mice
- Animals
- DNA/metabolism*
- Fibroblasts/metabolism
- Apoptosis Regulatory Proteins/metabolism
- Lysosomes/metabolism
- Memory, Long-Term/physiology*
- PubMed
- 32876528 Full text @ Autophagy
Citation
González-Rodríguez, P., Cheray, M., Füllgrabe, J., Salli, M., Engskog-Vlachos, P., Keane, L., Cunha, V., Lupa, A., Li, W., Ma, Q., Dreij, K., Rosenfeld, M.G., Joseph, B. (2020) The DNA methyltransferase DNMT3A contributes to autophagy long-term memory. Autophagy. 17(5):1259-1277.
Abstract
Macroautophagy/autophagy is a conserved catabolic pathway that targets cytoplasmic components for their degradation and recycling in an autophagosome-dependent lysosomal manner. Under physiological conditions, this process maintains cellular homeostasis. However, autophagy can be stimulated upon different forms of cellular stress, ranging from nutrient starvation to exposure to drugs. Thus, this pathway can be seen as a central component of the integrated and adaptive stress response. Here, we report that even brief induction of autophagy is coupled in vitro to a persistent downregulation of the expression of MAP1LC3 isoforms, which are key components of the autophagy core machinery. In fact, DNA-methylation mediated by de novo DNA methyltransferase DNMT3A of MAP1LC3 loci upon autophagy stimulation leads to the observed long-term decrease of MAP1LC3 isoforms at transcriptional level. Finally, we report that the downregulation of MAP1LC3 expression can be observed in vivo in zebrafish larvae and mice exposed to a transient autophagy stimulus. This epigenetic memory of autophagy provides some understanding of the long-term effect of autophagy induction and offers a possible mechanism for its decline upon aging, pathological conditions, or in response to treatment interventions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping