Dr. Ali Mortazavi
Nicole El-Ali, Ricardo Ramirez,
Camden Jansen, Marissa Macchietto,
Rabi Murad, Shan "Mandy" Jiang,
Weihua "Benny" Zeng, Eddie Park
Mortazavi Lab at UC Irvine
Department of Developmental and Cell Biology
Center for Complex Biological Systems
Applications of genomics, computation, and sequencing technologies to the analysis of transcriptional regulation in development.
We explore how gene regulatory networks that underlie development are encoded in the human genome, and we seek to understand their “grammar” using both laboratory and computational methods. We focus on how tissue-specific transcriptional enhancers work, and whether their expression levels and target genes can be predicted from in vivo protein-DNA interactions (as measured using ChIP-seq) and RNA expression (from RNA-seq) of both normal and perturbed differentiation time courses. No reliable computational methods yet exist to link distal enhancers to their target genes (which can be many genes and up to a megabase-pair away in mammals) using sequence, expression or ChIP-data alone.
While this identification problem is extremely difficult when considering large and complex genomes linearly, it would be a relatively easy problem if we could capture the three-dimensional interaction of the looping enhancers with their target promoters. We are, therefore, working with techniques that capture long-range chromatin interactions globally, such as ChIA-PET, in developmental time courses in order to integrate these long-range data with ChIP-seq and RNA-seq into testable gene regulatory networks. We are also interested in what fraction of these long-range interactions account for phenotypic variation between individuals and whether they are more likely to be conserved in vertebrates.