Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes

Mol Syst Biol. 2007:3:109. doi: 10.1038/msb4100151. Epub 2007 May 8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Line
  • Crosses, Genetic
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental*
  • Genes, myc*
  • Genotype
  • Gestational Age
  • Humans
  • Kidney
  • Lung / embryology*
  • Lung / growth & development*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Morphogenesis / genetics
  • Mutation
  • Pregnancy
  • Protein Interaction Mapping
  • Proteomics
  • Proto-Oncogene Proteins c-myc / deficiency
  • Proto-Oncogene Proteins c-myc / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, IGF Type 2 / genetics
  • Recombinant Fusion Proteins / analysis
  • Subcellular Fractions / metabolism
  • Transcription, Genetic
  • Transfection

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Receptor, IGF Type 2
  • Recombinant Fusion Proteins