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Variation in Regulatory Information Within and Between Species

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Maps chromatin marks in 19 people and finds enhancer marks most variable while promoters are more stable; activity frequently toggles on/off but enhancers rarely convert to promoters, and many variable sites link to motif-disrupting SNPs and show partial heritability. Measures ~6,000 proteins across ~90 lymphoblastoid lines by TMT mass spec, finds ~6% of proteins vary and about half of pQTLs overlap eQTLs while the rest act post‑transcriptionally. In yeast a single amino‑acid in YRR1 shifts NQO resistance and partner binding, producing a broad transcriptional program change.

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  1. 0:00Variation Regulatory Information within and Between Species
  2. 0:34Topics 1. Variation in regulatory information among humans - Protein levels 2. Master variators: linking
  3. 1:22What is the Difference Between People and Between Species? Coding Sequences vs Regulation
  4. 1:51Many Studies Have Demonstrated that Gene Expression Differs Among Individuals and Species Among humans 1 Microarrays: Stranger, Dermitzakis et al. Science (2007), PloS Genetics (2005), Nature
  5. 3:03Extensive Differences in TF Binding Between Species
  6. 4:14Variability in NFKappaB and Polll loci in Humans
  7. 4:56Additional Fundamental Questions?
  8. 6:00Histone Marks Representing a Variety of Functional Elements promoter
  9. 9:48Chromatin States Learned on 19 Individuals
  10. 12:07State Specific Variability of Chromatin Marks
  11. 17:04Chromatin Marks are Highly Heritable
  12. 18:50Functional Consequences of Chromatin Variation
  13. 20:31Map Protein Variation Across Individuals Map Relative Protein levels Across 90 LC Lines Using TMT Labeling
  14. 24:09Identify 77 pQTLs with 10%FDR; 273 with 30% FDR
  15. 27:30Personal Phenotypes: Variation in Chemical Response
  16. 29:02Genome-wide analysis study finds one region linked to NQO response
  17. 31:00Allele swap
  18. 35:30Comparing Mouse and Human with Mouse ENCODE Data
  19. 41:34Conservation of occupancy by GATA factors predicts enhancers active in multiple tissues
  20. 42:43Much of the biochemical activity covering a substantial portion of the genome is low level
  21. 43:24Higher signals for biochemical activity in more conserved genomic regions
  22. 44:09Acknowledgements
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