Ma 2018 Nat Cell Biol
|Ma C, Niu R, Huang T, Shao LW, Peng Y, Ding W, Wang Y, Jia G, He C, Li CY, He A, Liu Y (2018) N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation. Nat Cell Biol [Epub ahead of print].|
Abstract: N6-methyldeoxyadenine (6mA), a major type of DNA methylation in bacteria, represents a part of restriction-modification systems to discriminate host genome from invader DNA. With the recent advent of more sensitive detection techniques, 6mA has also been detected in some eukaryotes[2-8]. However, the physiological function of this epigenetic mark in eukaryotes remains elusive. Heritable changes in DNA 5mC methylation have been associated with transgenerational inheritance of responses to a high-fat diet, thus raising the exciting possibility that 6mA may also be transmitted across generations and serve as a carrier of inheritable information. Using Caenorhabditis elegans as a model, here we report that histone H3K4me3 and DNA 6mA modifications are required for the transmission of mitochondrial stress adaptations to progeny. Intriguingly, the global DNA 6mA level is significantly elevated following mitochondrial perturbation. N6-methyldeoxyadenine marks mitochondrial stress response genes and promotes their transcription to alleviate mitochondrial stress in progeny. These findings suggest that 6mA is a precisely regulated epigenetic mark that modulates stress response and signals transgenerational inheritance in C. elegans.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration, nDNA;cell genetics
Organism: Caenorhabditis elegans
Preparation: Intact cells
- Heyn H, Esteller M (2015) An adenine code for DNA: a second life for N6-methyladenine. Cell 161:710–13.
- Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y (2015) DNA methylation on N6-adenine in C. elegans. Cell 161:868–78.
- Zhang G, Huang H, Liu D, Cheng Y, Liu X, Zhang W, Yin R, Zhang D, Zhang P, Liu J, Li C, Liu B, Luo Y, Zhu Y, Zhang N, He S, He C, Wang H, Chen D (2015) N6-methyladenine DNA modification in Drosophila. Cell 161:893–906.
- Koziol MJ, Bradshaw CR, Allen GE, Costa ASH, Frezza C, Gurdon JB (2016) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23:24–30.
- Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ (2016) DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature 532:329–33.
- Liu J, Zhu Y, Luo GZ, Wang X, Yue Y, Wang X, Zong X, Chen K, Yin H, Fu Y, Han D, Wang Y, Chen D, He C (2016) Abundant DNA 6mA methylation during early embryogenesis of zebrafish and pig. Nat Commun 7:13052.
- Yao B, Cheng Y, Wang Z, Li Y, Chen L, Huang L, Zhang W, Chen D, Wu H, Tang B, Jin P (2017) DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress. Nat Commun 8:1122.
- Xiao CL, Zhu S, He M, Chen, Zhang Q, Chen Y, Yu G, Liu J, Xie SQ, Luo F, Liang Z, Wang DP, Bo XC, Gu XF, Wang K, Yan GR (2018) N(6)-methyladenine DNA modification in the human genome. Mol Cell 71:306–18.
- Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467:963–66.