Le paysage épigénétique…et le hasard
Jonathan Weitzman
Le hasard, le calcul et la vieCerisy 2019
Monod
« Les êtres vivants sont des machines chimiques. La croissance et la multiplication de tous les organismes exigent que soient accomplies des milliers de réactions chimiques grâce à quoi sont élaborés les constituants essentiels des cellules. »
Monod
« .. the ‘dream’ (as François Jacob has put it) of every cell: to become two cells. »
Epigenetics is being heralded as a scientific revolution
1940s-50s
The century of the gene
1866 1905 1911 1944 1953 1953
1970
Watson Crick
Protein
RNA
DNA
Phenotype
ProteinRNA
Gene
central dogma of molecular biology
Human Genome Project2001
3000 000 000 nucléotides
2,7 $ milliards
« The Book of Life »
3 000 000 000 lettres
a g c t
the human genome
2 997 000 000
a g c t
3 000 000
We
ssex
Reg
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Ce
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personalized genomics
Monod
« Tout ce qui est vrai pour la bactérie Escher ichia coli est vrai pour l’éléphant. »
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There are numerous examples of different phenotypes with the same genotype
divisionfusion jumeaux
du hasard?
Which professor Weitzman…?
1940s-50s
Advances in epigenetics research have paralleled genetics
1866 1953 1970
2012
2001
Waddington
“But between genotype and
phenotype lies a whole complex of
development processes”
Conrad Hal Waddington1905 –1975
epigenetics is ''the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being.''
Waddington coined the term epigenetics in the 1940s
the theory that embryonic development is due to a series of causal interactions between the various parts; the development of individual
organic form from the unformed Aristotle, 4th Century BCE
Embryogenesis is an increase in size of preformed structures already present in egg … or even in the sperm.« Homunculus »
epigenesis preformation
epigenetic processes: « As is a crystal, the structure of the assembled molecules itself constitutes the source of ‘information’ for the construction of the whole. »
« This analysis plainly reduces the old dispute between preformationists and epigeneticists to a quibble over words… The necessary information was present, but unexpresssed, in the constituents. The epigenetic building of a structure is not a creation; it is a revelation. »
1959
Waddington introduced the metaphor of the epigenetic landscape
Waddington himself was vague about theepigenetic landscape metaphor
1959
« Although the epigenetic landscape only provides a rough and ready
picture of the developing embryo, and cannot be interpreted rigorously, it has
certain merits for those who, like myself, find it comforting to have some
mental picture, however vague, for what they are trying to think about »
Nanney’s epigenetic control systems
PNAS 1958"Cellular memory"
The definition is constantly evolving
Robin Holliday1932 –2014
epigenetics is ‘the study of the changes in gene expression which occur in organisms with differentiated cells and the mitotic inheritance of given patterns of gene expression.'‘
Somatically heritable though cellular division
1959
Waddington introduced the metaphor of the epigenetic landscape
1959
Waddington speculated about the mechanisms underlying the epigenetic landscape
What’s in the epigenetic toolbox?
Cytosine 5methyl-Cytosine
DNA methylation is an epigenetic mark
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DNA methylation contributes to phenotypic variation
How to bee-come a Queen
Génétique Epi-génétique ?
How to bee-come a Queen
Waterland & Jirtle 2003
Nutritional supplements can impact DNA methylation and phenotypes (vitamin B12/Folate)
The availability of dietary methyl donors affects methylation of the yellow agouti locus
you are what you eat
Proc Natl Acad Sci U S A. 2005
Twin studies reveal that the environment may impact our epigenome throughout life
Genome 2m DNA
Nucleus5μm diameter
15000 km spaghetti Basket ball
Nucleosomes allow 10,000-fold compaction of DNA
euchromatin heterochromatin
ouvertaccessible
ferméeinaccessible
Epigenetic mechanisms control genome functionality
chromatin changes during the lifetime of MZ twins
Histone H4acetylation
Histone H3acetylation
Histone acetylation changes over one’s lifetime
The epigenome as a readout of metabolism
Acetyl coA
S adenosyl Methionine (SAM)
ATP
Environmental influences may be prenatal or postnatal
Encyclopedia of DNA Elements (ENCODE)Nature : 6 september 2012
le paysage épigénétiqueAny position on the epigenetic landscape can be described in terms of epigenome characteristics
We are learning to manipulate the epigenetic landscape
Tomorrow we will use epigenetic knowledge to treat disease
Image courtesy of Shutterstock
Nature vs Nurture
Hasard génétique Hasard epigénétique
Le paysage épigénétique…et le hasard
Jonathan Weitzman
Le hasard, le calcul et la vieCerisy 2019
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