Journal of Clinical Epigenetics Open Access

Potential new role for ROS in the epigenetic regulation of gene expression

2^nd International Congress on Epigenetics & Chromatin

November 06-08, 2017 | Frankfurt, Germany

Maria Inmaculada Calvo Sanchez ; Fernandez-Martos, S; Mjoseng HK; Fernandez-Crespo R; Meehan, RR; Espada, J.

Ramon y Cajal Institute for Biomedical Research (IRYCIS), Ramon y Cajal University Hospital, Madrid
MRC Human Genetics Unit at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh

Posters & Accepted Abstracts: J Clin Epigenet

Abstract:

The generation of Reactive Oxygen Species (ROS) as by-products of the highly efficient aerobic metabolism constitute an inescapable biochemical side effect that can be extremely harmful for cell viability, due to the irreversible oxidation of lipids, proteins and nucleic acids. Nevertheless, eukaryotic cells can also actively generate ROS as essential components of molecular mechanisms regulating key cellular processes, including proliferation and differentiation, through the oxidation of redox-sensitive proteins such as kinases and phosphatases. ROS production in ESCs is low as anaerobic glycolysis rather than oxidative phosphorylation (OxPhos) is favoured. A switch from glycolysis to OxPhos is observed during ESC differentiation and accumulating evidence suggests that ROS is an important signalling molecule for ESC differentiation. Here we propose that eukaryotic cells could use ROS to directly regulate DNA methylation and gene expression patterns through the oxidation of methylated cytosines at target gene promoters. To test this hypothesis, we have used a Protoporphyrin IX-dependent photodynamic treatment (PT) tool to activate a transient production of non-lethal ROS levels in the feeder-independent E14 mouse embryonic stem cell line. Using this tool, we report that the endogenous production of non-lethal ROS levels promotes a cytosine demethylation of tested promoters suggesting that these oxygen derivatives may be involved in the regulation of gene expression patterns through the dynamic modulation of DNA methylation patterns. Recent Publications 1. Thomson JP, Meehan RR. The application of genome-wide 5-hydroxymethylcytosine studies in cancer research. Epigenomics 2017, 9:77-91 2. Cole JJ et al. Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol 2017, 18:58. 3. Thomson JP et al. Loss of Tet1-Associated 5-Hydroxymethylcytosine Is Concomitant with Aberrant Promoter Hypermethylation in Liver Cancer. Cancer Res 2016, 76:3097-3108. 4. Nestor CE et al. 5-hydroxymethylcytosine remodeling precedes lineage specification during differentiation of human CD4+ T-cells. Cell Reports 2016, 16:559-570. 5. Carrasco E et al. Switching on a transient endogenous ROS production in mammalian cells and tissues. Methods. 109:180, 2016. 6. Fonda-Pascual P et al. In situ production of ROS in the skin by PDT as a powerful tool in clinical dermatology. Methods. 109:190, 2016. 7. Carrasco E et al. Photoactivation of ROS Production in Situ Transiently Activates Cell Proliferation in Mouse Skin and in the hair Follicle Stem Cell Niche Promoting Hair Growth and Wound Healing. Journal of Investigative Dermatology. 135:11, 2015. 8. Nestor CE et al. Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems. Genome Biol 2015, 16:11. 9. Bl�?¡zquez-Castro A et al. Protoporphyrin IX-dependent photodynamic production of endogenous ROS stimulates cell proliferation. European Journal of Cell Biology. 91:216, 2012. 10. Juarranz A et al. Mitotic catastrophe is implicated in the resistance of basal carcinoma cells to photodynamic therapy. Journal of Investigative Dermatology. 2012. 11. Espada J et al. Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context. Nucleic Acids Research. 39:9194, 2011

Biography :

Maria Inmaculada Calvo Sanchez holds a postdoc position in the Experimental Dermatology and Skin Biology Group of the IRYCIS, Ram�?³n y Cajal University Hospital. The research of this group is focused on cutaneus regenerative medicine and epigenetic changes induced by reactive oxygen species. Also she collaborates with the Francisco de Vitoria University as an associate professor in the degree of Biotechnology and in the Master's Degree in Advanced Therapies and Biotechnology Innovation, and as a coordinator of the practical part of the Masters mentioned above.