Towards the elucidation of the regulatory network guiding the insulin producing cells' differentiation

Genomics. 2012 Oct;100(4):212-21. doi: 10.1016/j.ygeno.2012.07.002. Epub 2012 Jul 20.


This study pertains to the regulatory network of neurogenin3 (NGN3, approved symbol: NEUROG3), the main regulator of insulin producing cells' formation. In silico regulatory region analyses of known and novel targets of NGN3 revealed the presence of two variants of a regulatory module that appeared conserved at the most phylogenetically distant species with pancreas. Both variants of this module contained binding sites of six transcription factors implicated in pancreas development. Nevertheless, an additional factor was found only into the module of the down-regulated by NGN3 genes. Whole genome analyses confirmed the statistical significance of these regulatory modules. Investigation of protein-protein interactions among the factors bound into these sequences indicated the formation of alternative protein complexes resulting into the up- or down-regulation of the respective genes. Subsequently, an NGN3-guided regulatory network, was modeled, describing the interactions among the analyzed genes with their transcriptional regulators, leading into the differentiation of cells capable of producing insulin.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • Basic Helix-Loop-Helix Transcription Factors* / metabolism
  • Binding Sites
  • Cell Differentiation* / genetics
  • Cell Differentiation* / physiology
  • Computational Biology
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Genome
  • Insulin Secretion
  • Insulin* / biosynthesis
  • Insulin* / genetics
  • Insulin* / metabolism
  • Insulin-Secreting Cells / metabolism
  • Mice
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Phylogeny
  • Protein Interaction Maps
  • Transcription Factors / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Insulin
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Transcription Factors