Structure and Evolution of Mammalian Gene Networks

Citation

Mortazavi, Ali (2008) Structure and Evolution of Mammalian Gene Networks. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/FT1Y-M657. https://resolver.caltech.edu/CaltechETD:etd-05292008-140438

Abstract

Accurate measurements of protein:DNA and RNA expression levels are critical to building meaningful models of gene regulatory networks. We develop here two new techniques doing such measurements using ultra-high-throughput DNA sequencing combined with extensive computational analyses, which we call respectively ChIP-seq and RNA-seq. To show the power and versatility of these techniques, we apply them to the study of two model problems that are representative of the research agenda of regulatory biology. We use ChIP-seq to study the conservation and evolution of the binding repertoire of the transcription factor NRSF/REST in boreoeutherian mammals, whereas we use ChIP-seq of RNA Polymerase II phosphoisoforms and RNA-seq to study a developmental time course of myogenesis in the C2C12 mouse cell line. Together, ChIP-seq and RNA-seq show the promise of ultra-high-throughout sequencing in mapping and studying gene regulatory networks which will likely supplant the previous generation of microarray-based technologies as the new generations of sequencers mature and become more generally available.

Thesis Files