Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes.
Although microarray analysis has provided information regarding the dynamics of gene expression during development of the mouse lung, no extensive correlations have been made to the levels of corresponding protein products. Here, we present a global survey of protein expression during mouse lung organogenesis from embryonic day E13.5 until adulthood using gel-free two-dimensional liquid chromatography coupled to shotgun tandem mass spectrometry (MudPIT). Mathematical modeling of the proteomic profiles with parallel DNA microarray data identified large groups of gene products with statistically significant correlation or divergence in coregulation of protein and transcript levels during lung development. We also present an integrative analysis of mRNA and protein expression in Nmyc loss- and gain-of-function mutants. This revealed a set of 90 positively and negatively regulated putative target genes. These targets are evidence that Nmyc is a regulator of genes involved in mRNA processing and a repressor of the imprinted gene Igf2r in the developing lung.
Cox
Brian
B
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada.
Kislinger
Thomas
T
Wigle
Dennis A
DA
Kannan
Anitha
A
Brown
Kevin
K
Okubo
Tadashi
T
Hogan
Brigid
B
Jurisica
Igor
I
Frey
Brendan
B
Rossant
Janet
J
Emili
Andrew
A
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007668:Kidney; D008168:Lung / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D025941:Protein Interaction Mapping; D040901:Proteomics; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000032:analysis; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D011993:Recombinant Fusion Proteins