Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells

Jared C. Roach, Kelly D. Smith, Katie L. Strobe, Stephanie M. Nissen, Christian D. Haudenschild, Daixing Zhou, Thomas J. Vasicek, G. A. Held, Gustavo A. Stolovitzky, Leroy E. Hood, Alan Aderem

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Transcription factors play a key role in integrating and modulating biological information. In this study, we comprehensively measured the changing abundances of mRNAs over a time course of activation of human peripheral-blood-derived mononuclear cells ("macrophages") with lipopolysaccharide. Global and dynamic analysis of transcription factors in response to a physiological stimulus has yet to be achieved in a human system, and our efforts significantly advanced this goal. We used multiple global high-throughput technologies for measuring mRNA levels, including massively parallel signature sequencing and GeneChip microarrays. We identified 92 of 1,288 known human transcription factors as having significantly measurable changes during our 24-h time course. At least 42 of these changes were previously unidentified in this system. Our data demonstrate that some transcription factors operate in a functional range below 10 transcripts per cell, whereas others operate in a range three orders of magnitude greater. The highly reproducible response of many mRNAs indicates feedback control. A broad range of activation kinetics was observed; thus, combinatorial regulation by small subsets of transcription factors would permit almost any timing input to cis-regulatory elements controlling gene transcription.

Original languageEnglish
Pages (from-to)16245-16250
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number41
DOIs
StatePublished - 9 Oct 2007
Externally publishedYes

Keywords

  • Gene expression microarray
  • Massively parallel signature sequencing
  • Systems biology
  • Transcript enumeration

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