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Transcript
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 • Main Mechanisms • DNA methylation • Histone modifications • RNAi-mediated heterochromatin formation Major Phenomena and Applications • • • • • Dosage compensation Genomic imprinting Position Effect Variegation Stem cell research (Regenerative Medicine) Cancer Genetics Evolutionary Conservation Historical perspectives • • • • • • • • • • • • • 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 • Transition from ‘non-mendelian oddity’ to mainstream ‘epigenetic field’
