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Epigenetics
Joomyeong ‘Joo’ Kim
Louisiana State University
What is Epigenetics?
• “the study of mitotically and/or meiotically
heritable changes in gene function that can
not be explained by changes in DNA
sequences” – (Riggs et al. 1996)
• originally was coined to describe “all the
developmental events leading to a mature
organism from a fertilized zygote” (Waddington, 1953)
Epigenetics vs Genetics
• DNA is not ‘naked’
• Reversible modifications
• Transitory marks
in response to intrinsic
and external stimuli
Significances (why so hot?)
• Challenging and revising traditional paradigm
of inheritance
• Providing tremendous levels of plasticity to
species for adaptation
(genome-hardware : epigenome-software)
• Reversible nature (stem cell research and
regenerative medicine)
Impact on Genetics
• Genotypes dictate Phenotypes (traditional)
• Environment can be a factor for the
inheritance pattern driven by genotype
Environment
Genotype
Phenotype
Impact on Evolution
Darwinian evolution (mutation-driven natural selection)
“random mutation”
“natural selection”
alleles
Lamarckian evolution (Transgenerational inheritance of epigenetic modification)
“environment”
“no mutation”
alleles
epialleles
Impact on Evolution
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Main Mechanisms
• DNA methylation
• Histone modifications
• RNAi-mediated heterochromatin formation
Major Phenomena and Applications
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Dosage compensation
Genomic imprinting
Position Effect Variegation
Stem cell research (Regenerative Medicine)
Cancer Genetics
Evolutionary Conservation
Historical perspectives
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1941 – HJ Muller (Position Effect Variegation in Drosophila)
1951 - McClintock (mutable loci in maize)
1953 – RA Brink (paramutation in maize)
1961 – M Lyon ( X inactivation in mammals)
1983 – H Cedar, W Doerfler (CpG methylation in promoter)
1985 – D Solter, A Surani, B Cattanach (Genomic imprinting in mammals)
1993 – A Bird (MeCp1), H Willard (Xist), S Tilghman (H19/Igf2)
Mid 1990 – Histone Acetylation and HAT and HDAC isolation
2000 – PcG – Histone Lysine Methylase
2001 – Jenuwein and Allis (Histone Code)
2004 – Histone Lysine Demethylase
2007 – Histone methylation – DNA methylation connection
2009 – DNA methylation demethylases
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Transition from ‘non-mendelian oddity’ to mainstream ‘epigenetic field’