Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics

被引：144

作者：

Ramsey, Stephen A. ^{[1
]}

Klemm, Sandy L. ^{[1
]}

Zak, Daniel E. ^{[1
]}

Kennedy, Kathleen A. ^{[1
]}

Thorsson, Vesteinn ^{[1
]}

Li, Bin ^{[1
]}

Gilchrist, Mark ^{[1
]}

Gold, Elizabeth S. ^{[1
]}

Johnson, Carrie D. ^{[1
]}

Litvak, Vladimir ^{[1
]}

Navarro, Garnet ^{[1
]}

Roach, Jared C. ^{[1
]}

Rosenberger, Carrie M. ^{[1
]}

Rust, Alistair G. ^{[1
]}

Yudkovsky, Natalya ^{[1
]}

Aderem, Alan ^{[1
]}

Shmulevich, Ilya ^{[1
]}

机构：

[1] Inst Syst Biol, Seattle, WA USA

来源：

PLOS COMPUTATIONAL BIOLOGY | 2008年 / 4卷 / 03期

关键词：

D O I：

10.1371/journal.pcbi.1000021

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophages are versatile immune cells that can detect a variety of pathogen-associated molecular patterns through their Toll-like receptors ( TLRs). In response to microbial challenge, the TLR-stimulated macrophage undergoes an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network poses significant challenges and requires the integration of multiple experimental data types. In this work, we inferred a transcriptional network underlying TLR-stimulated murine macrophage activation. Microarray-based expression profiling and transcription factor binding site motif scanning were used to infer a network of associations between transcription factor genes and clusters of co-expressed target genes. The time-lagged correlation was used to analyze temporal expression data in order to identify potential causal influences in the network. A novel statistical test was developed to assess the significance of the time-lagged correlation. Several associations in the resulting inferred network were validated using targeted ChIP-on-chip experiments. The network incorporates known regulators and gives insight into the transcriptional control of macrophage activation. Our analysis identified a novel regulator ( TGIF1) that may have a role in macrophage activation.

引用

页数：25

共 96 条

[91] Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle [J].