hlh-1 and the C. elegans Body Wall Muscle Transcriptional Differentiation Network

Author: Kuntz, Steven Gregory

Year: 2011

Degree: Dissertation (Ph.D.)

Advisors: Wold, Barbara J.; Sternberg, Paul W.

Committee Members: Elowitz, Michael B.; Rothenberg, Ellen V.; Stathopoulos, Angelike; Wold, Barbara J.; Sternberg, Paul W.

Option: Biochemistry and Molecular Biophysics

DOI: 10.7907/18XS-YM65

Abstract

To understand the structure and function of gene regulatory networks, it is important to first catalogue the components. Measurable constituents of networks include cis-regulatory elements, identified by their conservation and ability to drive expression; transcription factor binding motifs, identified by protein binding; transcription factors, identified by their necessity in network function; and target genes, identified by their conditional expression. The heart of a regulatory network is the transcription factor, which is dedicated to its role in the network. Transcription factors must be activated and regulate downstream targets in a discrete and reproducible fashion. Any deviation in network function may result in the collapse of the network and death of the animal. Thus, a network must be robust enough to function under a variety of biological conditions. However, network redundancies are inefficient in terms of fitness and lost during the course of evolution. The network structure and function reflects these evolutionary realities: strong sequence conservation of cis-regulatory elements coupled with widespread stochastic transcription factor binding, and ancient transcription factor conservation coupled with overlapping activation of targets. The evolution of functional transcription factor networks therefore must be a balance between conservation and flexibility.

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