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Genome-wide Identification of Craniofacial Transcriptional Enhancers. Axel Visel Genomics Division Lawrence Berkeley Nat’l Lab. Motivation: To understand the genetics of craniofacial development and clefting disorders, we must understand distant-acting gene regulation. Challenge 1 :
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Genome-wide Identification ofCraniofacial Transcriptional Enhancers Axel Visel Genomics Division Lawrence Berkeley Nat’l Lab Motivation: To understand the genetics of craniofacial development and clefting disorders, we must understand distant-acting gene regulation Challenge 1: Non-coding GWAS hits Example: 8q24 Challenge 2: Complex regulatory architecture Msx1 protein (nLacZ, Coudert et al.) Distal enhancers (Visel, unpublished) -75kb -95kb -140kb -230kb enhancer hCF154 MYC PVT1 640kb NSCL/P risk interval Msx1 Stx18 (Birnbaum et al. 2009) Tools 1. Tissue-ChIP-seq to FIND enhancers in the genome 2. CHARACTERIZE craniofacial enhancer activities in transgenic mice
Genome-wide Identification ofCraniofacial Transcriptional Enhancers Axel Visel Genomics Division Lawrence Berkeley Nat’l Lab Progress (Year 1) Data Workflow collect face/palate tissues genome-wide sets of candidate enhancers and matched expression data peak coordinates “wiggle tracks” expression profiles ChIP-seq: E11.5 face available E13.5 palate in progress RNA-seq: first data for E12.5/E14.5 p300 ChIP-seq + RNA-seq test candidate enhancers in transgenic mice results of transgenic mouse assays 25-30 candidate sequences/yr whole-mount photos OPT data transgenics: 30 candidates testing done (reference or mouse alleles) GWAS/resequencing follow-ups: candidate regions in progress (8q24, Twist1) test known risk variants OPT data
