Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells.
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.
Roach
Jared C
JC
Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA. jroach@systemsbiology.org
Smith
Kelly D
KD
Strobe
Katie L
KL
Nissen
Stephanie M
SM
Haudenschild
Christian D
CD
Zhou
Daixing
D
Vasicek
Thomas J
TJ
Held
G A
GA
Stolovitzky
Gustavo A
GA
Hood
Leroy E
LE
Aderem
Alan
A
D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D049490:Systems Biology; D014157:Transcription Factors / Q000235:genetics*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014157:Transcription Factors