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Structure and evolution of mammalian gene networks


Mortazavi, Ali (2008) Structure and evolution of mammalian gene networks. Dissertation (Ph.D.), California Institute of Technology.


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.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:ChIP-seq; ChIPSeq; CTD; NRSE; NRSF; polymerase; REST; RNA-seq; ultra-high-throughput
Degree Grantor:California Institute of Technology
Major Option:Biology
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Wold, Barbara J.
Thesis Committee:
  • Rothenberg, Ellen V. (chair)
  • Wold, Barbara J.
  • Davidson, Eric H.
  • Sternberg, Paul W.
Defense Date:15 May 2008
Record Number:CaltechETD:etd-05292008-140438
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2260
Deposited By: Imported from ETD-db
Deposited On:02 Jun 2008
Last Modified:26 Dec 2012 02:49

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