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