NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene

Mol Cell Biol. 1997 Nov;17(11):6673-82. doi: 10.1128/MCB.17.11.6673.

Abstract

NeuroD1/beta2 is a basic helix-loop-helix (bHLH) factor expressed in the endocrine cells of the pancreas and in a subset of neurons as they undergo terminal differentiation. We now show that NeuroD1 is expressed in corticotroph cells of the pituitary gland and that it is involved in cell-specific transcription of the proopiomelanocortin (POMC) gene. It was previously shown that corticotroph-specific POMC transcription depends in part on the action of cell-restricted bHLH factors that were characterized as the CUTE (corticotroph upstream transcription element) (M. Therrien and J. Drouin, Mol. Cell. Biol. 13:2342-2353, 1993) complexes. We now demonstrate that these complexes contain NeuroD1 in association with various ubiquitous bHLH dimerization partners. The NeuroD1-containing heterodimers specifically recognize and activate transcription from the POMC promoter E box that confers transcriptional specificity. Interestingly, the NeuroD1 heterodimers activate transcription in synergy with Ptx1, a Bicoid-related homeodomain protein, which also contributes to corticotroph specificity of POMC transcription. In the adult pituitary gland, NeuroD1 transcripts are detected in POMC-expressing corticotroph cells. Taken together with the restricted pattern of Ptx1 expression, these results suggest that these two factors establish the basis of a combinatorial code for the program of corticotroph-specific gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / genetics
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Gene Expression Regulation, Developmental
  • Helix-Loop-Helix Motifs
  • Homeodomain Proteins / metabolism
  • Models, Biological
  • Nerve Tissue Proteins / metabolism*
  • Paired Box Transcription Factors
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Pro-Opiomelanocortin / biosynthesis
  • Pro-Opiomelanocortin / genetics*
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid
  • Tissue Distribution
  • Trans-Activators / metabolism*
  • Transcription Factors / classification
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Paired Box Transcription Factors
  • Trans-Activators
  • Transcription Factors
  • homeobox protein PITX1
  • Neurogenic differentiation factor 1
  • Pro-Opiomelanocortin