2 / 22
Page 90
conferenceseries
.com
Volume 3, Issue 4
J Clin Epigenet
ISSN: 2472-1158
Epigenetics 2017
November 06-08, 2017
EPIGENETICS & CHROMATIN
November 06-08, 2017 | Frankfurt, Germany
2
nd
International Congress on
Potential new role for ROS in the epigenetic regulation of gene expression
María Inmaculada Calvo Sánchez 1; Fernandez-Martos, S1; Mjoseng HK2; Fernandez-Crespo R1; Meehan, RR2; Espada, J. 1
1
Ramón y Cajal Institute for Biomedical Research (IRYCIS), Ramón y Cajal University Hospital, Madrid
2
MRC Human Genetics Unit at the Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh
T
he 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 StemCell Niche Promoting Hair Growth andWound 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. Blázquez-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.
Benjamin Gonzalez Lopez, J Clin Epigenet 2017, 3:4
DOI: 10.21767/2472-1158-C1-003