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Genomics of Transcriptional Regulation. Ken Daigoro Yokoyama Pollock lab. Why study regulation?. Directs complex processes Cross-species differences Not well understood. Overview. Promoter architecture Cis-regulatory element discovery Gene networks. Transcription.
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Genomics ofTranscriptional Regulation • Ken Daigoro Yokoyama • Pollock lab
Why study regulation? • Directs complex processes • Cross-species differences • Not well understood
Overview • Promoter architecture • Cis-regulatory element discovery • Gene networks
Promoter architecture • Core promoter elements • Proximal promoter elements • Regulatory modules • Enhancers / Silencers
Promoter elements TATA Upstream elements Inr Downstream elements
Broad vs Single peakPromoters Single peak
Broad vs Single peakPromoters Single peak Broad peak
Dinucleotide composition GC AT
Functional motif discovery • Functional elements : ~20% noncoding DNA • Typically short : 6-12 bp • Degenerate sites
Position weight matrices (PWMs) A C G T G/C T A T A A/T A A/T
De novoMotif prediction • Input : Small set of promoters • Coregulation = Cooccurrence • Several user-defined parameters
Phylogenetic footprinting • Cross-species comparisons • Alignment-based • Highly conserved sequence elements
Phylogenetic footprinting Human Macaque Mouse Rat Dog Cow Dodo Bird GWBush Frog Fish
Promoter evolution • Sequence conservation vs Regulation • Alignments • Consensus sequence evolution
Gene networks • Development, Differentiation, Apoptosis, Cancer progression • Complex relationships • Protein-protein-DNA interactions
Gene networks A B C
Transcriptional activation A B AND
Transcriptional activation A B AND A B OR
Transcriptional activation A B AND ON / OFF (Continuous) A B A B OR
Transcriptional repression A B C C
Transcriptional repression A B C C
Transcriptional repression A B C A B
Transcriptional repression A B C A C B
Transcriptional repression A B C A B B C
Transcriptional repression A B C A B B C
Transcriptional repression A B C A B C