NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene.
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.
Poulin
G
G
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, Québec, Canada.
Turgeon
B
B
Drouin
J
J
D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000145:classification / Q000378:metabolism*; D019281:Dimerization; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051761:Paired Box Transcription Factors; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics*; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000145:classification / Q000378:metabolism; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; D011333:Pro-Opiomelanocortin; D015534:Trans-Activators; D014157:Transcription Factors; C101485:homeobox protein PITX1; C093564:Neurogenic differentiation factor 1