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Comparative Epigenomics 1/2 Ga ë l YVERT Ecole Normale Sup é rieure de Lyon CNRS France

Comparative Epigenomics 1/2 Ga ë l YVERT Ecole Normale Sup é rieure de Lyon CNRS France. Sketch. Introduction Single-Nucleosome Epi-Polymorphisms in Yeast Genetic basis of SNEPs. Chromatin Epigenomics. Chromatin Epigenetics. Heritability of genotypes changing chromatin topology/dynamics

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Comparative Epigenomics 1/2 Ga ë l YVERT Ecole Normale Sup é rieure de Lyon CNRS France

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  1. Comparative Epigenomics1/2Gaël YVERTEcole Normale Supérieure de LyonCNRSFrance

  2. Sketch • Introduction • Single-Nucleosome Epi-Polymorphisms in Yeast • Genetic basis of SNEPs

  3. Chromatin Epigenomics

  4. Chromatin Epigenetics • Heritability of genotypes changing chromatin topology/dynamics • Imprinting • Transgenerational Epigenetic Inheritance • Somatic Epigenetics

  5. in trans: Rett syndrome HDAC MeCP2 Histone Acetylation and Transcription Me Me Me Me Me Genotypes affecting chromatin states in cis: Fragile-X mutation CGG CGG CGG CGG CGG CGG FMR1 gene 200 Me Me Me Me Me Me Me Me

  6. Prader-Willi Syndrome Angelman Syndrome Imprinting 15q11-q13 locus: ZNF127 NDN IC SNRPN UBE3A GABR genes + + + + + + + +/- + + + Paternal: Expression - - - - - - - + + + + Maternal:

  7. Mothers on Diet with Methyl Precursors Methylation Waterland & Jirtle MolCellBiol 2003 Transgenerational Epigenetic Inheritance IAP retro-transposon ectopic transcription Avy allele Me Me Me Agouti gene

  8. Re-visiting J-B Lamarck? 1744-1829 ‘an adaptive force’ Practise -> Adaptation -> Transmission of adaptive trait to offspring Environment -> Physiological Change -> Transmission to offspring Diet -> Epigenetic Change -> Heritable Epigenetics

  9. Somatic Epigenetics Mikkelsen et al. Nature 2008

  10. Chromatin Epigenetics • Heritability of genotypes changing chromatin topology/dynamics • Imprinting • Transgenerational Epigenetic Inheritance • Somatic Epigenetics

  11. Sketch • Introduction • Single-Nucleosome Epi-Polymorphisms in Yeast • Genetic basis of SNEPs

  12. C G What makes the difference ?

  13. Epigenomic Profiling MNase genome tiling array All Nucleosomes

  14. ChIP genome tiling array Marked Nucleosomes Epigenomic Profiling MNase genome tiling array All Nucleosomes

  15. Comparison of 2 S. cerevisiae strains BY ~ S288c: laboratory, rotten fig (sequenced & assembled) - mapping: 3 replicates - H3K14ac: 6 replicates RM: haploid from vinyard isolate (sequenced & assembled) - mapping: 3 replicates - H3K14ac: 6 replicates Transcriptome already compared in standardized lab environment Analysis: NucleoMiner

  16. Nucleosome Positioning

  17. Hidden Markov Model Science 2005

  18. Hidden Markov Model Science 2005

  19. Hidden Markov Model Science 2005

  20. Genome alignments Map probes (single, perfect match) on each genome Use maximum probes on each genome Fit HMM parameters for each strain

  21. Nucleosome Positioning HMM as in Yuan et al. Science 2005 Lee et al. Nature Genetics 2007

  22. Nucleosome Positioning HMM as in Yuan et al. Science 2005 Lee et al. Nature Genetics 2007

  23. RM BY Positioning is conserved

  24. Screen for Single Nucleosome Epi-Polymorphisms (SNEP) ANOVA model: yijkl = u + Si + Ej + Pk + SxEij + eijkl Si = {BY, RM} Ej = {nuc, H3K14ac} Probe k

  25. 5,442 SNEP found at FDR=0.0001 Screening for SNEP 58,694 nucleosomes interrogated

  26. H3 K14ac SNEP

  27. Ty position effects

  28. Ty position effects

  29. rDNA position effect

  30. rDNA position effect

  31. Isolated or clustered?

  32. Isolated or clustered? 55% are ‘isolated’

  33. Different profiles

  34. Different profiles: not explaining all SNEPs

  35. BYac SNEP hit regulatory elements evol conservation

  36. Correlation to expression divergence?

  37. SNEP correlation with plasticity

  38. More SNEPs in ‘plastic’ genes

  39. 2008 147 nucleosomes remodeled: 1.7 fold enrichment of SNEP (P = 0.01)

  40. C C T T What in the diploid hybrid? ?

  41. C T Allele-Specificity C MNase Seq C C ChIP T 12 Million Solexa Reads Test Allele-Specificity for 2,327 SNEPs 128 Allele-Specific SNEPs (108 far from Ty, rDNA or Telomere)

  42. Allele-Specificity Poor correlation with parental difference

  43. Maud de Dieuleveult X. Gidrol, CEA Evry L. Steinmetz, EMBL ProfilExpert, Lyon Lyon Grants: ATIP (CNRS), ANR Acknowledgments Jean-Baptiste Veyrieras M. Nagarajan Helene Bottin Anne-Laure Abraham

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