Integrated Genomic and Proteomic Analyses of Gene Expression in Mammalian Cells*S

Using DNA microarrays together with quantitative proteomic techniques (ICAT reagents, two-dimensional DIGE, and MS), we evaluated the correlation of mRNA and protein levels in two hematopoietic cell lines representing distinct stages of myeloid differentiation, as well as in the livers of mice treated for different periods of time with three different peroxisome proliferative activated receptor agonists. We observe that the differential expression of mRNA (up or down) can capture at most 40% of the variation of protein expression. Although the overall pattern of protein expression is similar to that of mRNA expression, the incongruent expression between mRNAs and proteins emphasize the importance of posttranscriptional regulatory mechanisms in cellular development or perturbation that can be unveiled only through integrated analyses of both proteins and mRNAs.

[1]  Stephen W. Edwards,et al.  Microarray Standard Data Set and Figures of Merit for Comparing Data Processing Methods and Experiment Designs , 2003, Bioinform..

[2]  J. Berger,et al.  5-Aryl thiazolidine-2,4-diones as selective PPARγ agonists , 2003 .

[3]  Min Pan,et al.  Coordinate regulation of energy transduction modules in Halobacterium sp. analyzed by a global systems approach , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Alexey I Nesvizhskii,et al.  Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. , 2002, Analytical chemistry.

[5]  L. Hood,et al.  Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae*S , 2002, Molecular & Cellular Proteomics.

[6]  David E. Misek,et al.  Discordant Protein and mRNA Expression in Lung Adenocarcinomas * , 2002, Molecular & Cellular Proteomics.

[7]  Rainer Cramer,et al.  Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System* , 2002, Molecular & Cellular Proteomics.

[8]  Nan Hu,et al.  2D Differential In-gel Electrophoresis for the Identification of Esophageal Scans Cell Cancer-specific Protein Markers* , 2002, Molecular & Cellular Proteomics.

[9]  Y. Li,et al.  Regulation of rat carboxylesterase expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): a dose-dependent decrease in mRNA levels but a biphasic change in protein levels and activity. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[10]  R. Aebersold,et al.  Quantitative profiling of differentiation-induced microsomal proteins using isotope-coded affinity tags and mass spectrometry , 2001, Nature Biotechnology.

[11]  Roger E Bumgarner,et al.  Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. , 2001, Science.

[12]  Yudong D. He,et al.  Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer , 2001, Nature Biotechnology.

[13]  Matthew Davison,et al.  Validation and development of fluorescence two‐dimensional differential gel electrophoresis proteomics technology , 2001, Proteomics.

[14]  R. Young,et al.  Biomedical Discovery with DNA Arrays , 2000, Cell.

[15]  J. M. Izquierdo,et al.  A Conserved Mechanism for Controlling the Translation of β-F1-ATPase mRNA between the Fetal Liver and Cancer Cells* , 2000, The Journal of Biological Chemistry.

[16]  T. Hughes,et al.  Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. , 2000, Science.

[17]  S. Gygi,et al.  Quantitative analysis of complex protein mixtures using isotope-coded affinity tags , 1999, Nature Biotechnology.

[18]  J. Lammers,et al.  Association of RACK1 and PKCβ with the common β-chain of the IL-5/IL-3/GM-CSF receptor , 1999, Oncogene.

[19]  V. Broudy,et al.  Stem cell factor and hematopoiesis. , 1997, Blood.

[20]  M. Ünlü,et al.  Difference gel electrophoresis. A single gel method for detecting changes in protein extracts , 1997, Electrophoresis.

[21]  S. Collins,et al.  Lymphohematopoietic progenitors immortalized by a retroviral vector harboring a dominant-negative retinoic acid receptor can recapitulate lymphoid, myeloid, and erythroid development. , 1994, Genes & development.

[22]  S. Collins,et al.  A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[23]  William H. Press,et al.  Numerical recipes in C (2nd ed.): the art of scientific computing , 1992 .

[24]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[25]  J. S. Hunter,et al.  Statistics for experimenters : an introduction to design, data analysis, and model building , 1979 .

[26]  Sidney Addelman,et al.  trans-Dimethanolbis(1,1,1-trifluoro-5,5-dimethylhexane-2,4-dionato)zinc(II) , 2008, Acta crystallographica. Section E, Structure reports online.