Transcriptome-based determination of multiple transcription regulator activities in Escherichia coli by using network component analysis

doi:10.1073/pnas.0305287101

Transcriptome-based determination of multiple transcription regulator activities in Escherichia coli by using network component analysis

Departments of ^*Chemical Engineering, ^†Electrical Engineering, ^‡Human Genetics, and ^§Statistics, University of California, Los Angeles, CA 90095

Edited by Lonnie O'Neal Ingram, University of Florida, Gainesville, FL, and approved October 29, 2003 (received for review August 19, 2003)

Abstract

Cells adjust gene expression profiles in response to environmental and physiological changes through a series of signal transduction pathways. Upon activation or deactivation, the terminal regulators bind to or dissociate from DNA, respectively, and modulate transcriptional activities on particular promoters. Traditionally, individual reporter genes have been used to detect the activity of the transcription factors. This approach works well for simple, non-overlapping transcription pathways. For complex transcriptional networks, more sophisticated tools are required to deconvolute the contribution of each regulator. Here, we demonstrate the utility of network component analysis in determining multiple transcription factor activities based on transcriptome profiles and available connectivity information regarding network connectivity. We used Escherichia coli carbon source transition from glucose to acetate as a model system. Key results from this analysis were either consistent with physiology or verified by using independent measurements.

Footnotes

↵ ¶ To whom correspondence should be addressed. E-mail: liaoj{at}ucla.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: TF, transcription factor; TFA, TF activity; NCA, network component analysis; TCA, tricarboxylic acid; CRP, catabolite repressor protein; CS, control strength.