Journal article
Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages
K Schroder, KM Irvine, MS Taylor, NJ Bokil, KA Le Cao, KA Masterman, LI Labzin, CA Semple, R Kapetanovic, L Fairbairn, A Akalin, GJ Faulkner, JK Baillie, M Gongora, CO Daub, H Kawaji, GJ McLachlan, N Goldman, SM Grimmond, P Carninci Show all
Proceedings of the National Academy of Sciences of the United States of America | Published : 2012
Abstract
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)-4 agonist lipopolysaccharide (LPS). By using a custom platform permitting crossspecies interrogation coupled with deep sequencing of mRNA 5′ends, we identified extensive divergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologues were identified as "divergently regulated"). We further demonstrate concordant regulation of human-specific LPS tar..
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Awarded by Medical Research Council
Funding Acknowledgements
We thank the Institute for Molecular Bioscience Special Research Centre Microarray Facility for performing the microarray hybridizations, as well as David Wood and Dr. Cas Simons (Queensland Facility for Advanced Bioinformatics, University of Queensland) for building the MacGate Web site. This work was supported by C. J. Martin Fellowship 490993 from the Australian National Health and Medical Research Council (to K.S.); Australian Research Council under the ARC Centres of Excellence program (ARC Centre of Excellence in Bioinformatics, K.-A.L.C.); Australian Research Council Future Fellowship FT100100657 (to M.J.S.); honorary Australian National Health and Medical Research Council Senior Research Fellowship APP1003470 (to M.J.S.); Australian National Health and Medical Research Council Grant 631531, a research grant to the RIKEN Omics Science Center from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); and an Innovative Cell Biology by Innovative Technology Project grant from MEXT (to Y.H.), which supported Cap Analysis of Gene Expression data collection and mapping.