What is epigenetics?

What is epigenetics?
Lode Godderis (Md, Phd)1,2
1
KULeuven, Center Environment and Health, Belgium;
2 Idewe, Heverlee, Belgium
Outline
•
•
•
•
•
Introduction
Objective
Impact environment on health through epigenetics
Impact environment on development through epigenetics
Conclusion
Introduction
Introduction
Introduction
“Heritable changes that regulate gene expression that occur
without change in nucleotide sequence”
5
Bird (Nature, 2007)
Outline
•
•
•
•
•
Introduction
Objective
Impact environment on health through epigenetics
Impact environment on development through epigenetics
Conclusion
Objective
Impact environment on health
through epigenetics
Impact environment on
development through epigenetics
Outline
•
•
•
•
•
Introduction
Objective
Impact environment on health through epigenetics
Impact environment on development through epigenetics
Conclusion
Impact environment on health through
epigenetics
Genetic mechanisms
Genetic mechanisms
• Mutagens
• Intercalating agents and
cross-linkers
• Clastogens
• Aneugens
Genetic mechanisms
• Proto-oncogene Oncogene
o Gain of function
o RAS, MYC
• Tumor suppressor gene
o
o
Loss of function
P53, APC
Response of cells
Response of cells
Godderis et al. (Plos One 2012)
Response of cells
Godderis et al. (Plos One 2012)
Response of cells
Response of cells
Godderis et al. (Plos One 2012)
Epigenetic mechanisms
Epigenetic mechanisms
• DNA methylation
• Histone modification
• Non-coding RNA
Epigenetic mechanisms
• DNA methylation
• Histone modification
• Non-coding RNA
Epigenetic mechanisms: gene-specific DNA
methylation
Epigenetic mechanisms: global DNA
methylation
Robertson (Nat Rev Genet, 2005 )
Epigenetic mechanisms: global DNA
methylation
Godderis et al. (Epigenomics, 2012)
Epigenetic mechanisms: global DNA
methylation
Godderis et al. (Epigenomics, 2012)
Epigenetic mechanisms: global DNA
methylation
5,4
% global DNA methylation
5,2
5
4,8
4,6
4,4
4,2
4
3,8
Epigenetic mechanisms: gene-specific DNA
methylation
8
p = 0.003
7
% DNA Methylation
6
5
4
3
2
1
0
Epigenetic mechanisms
• DNA methylation
• Histone modification
• Non-coding RNA
Epigenetic mechanisms: histone modification
Schones and Zhao (Nature Revi Gen, 2008)
Epigenetic mechanisms
Dik et al. (Crit Rev in Tox, 2012)
Epigenetic mechanisms
• DNA methylation
• Histone modification
• Non-coding RNA
Epigenetic mechanisms: non coding RNA
Esquela-Kerscher and Slack (Nature Reviews Cancer, 2006)
Epigenetic mechanisms
Sandoval and Esteller (Cur Opin in Gen and Dev, 2012)
Outline
•
•
•
•
Introduction
Objective
Impact environment on health through epigenetics
Impact environment on development through
epigenetics
• Conclusion
Impact environment on development through
epigenetics
Epigenetics, a natural mechanism
Impact environment on development through
epigenetics
Cradle and environment do matter
Cradle and environment do matter
Outline
•
•
•
•
•
Introduction
Objective
Impact environment on health through epigenetics
Impact environment on development through epigenetics
Conclusion
Conclusion
Conclusion
Thanks to: Prof dr P. Hoet, dr Katrien Poels, A.Tabish, S Pauwels