| First Author | Demarco IA | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 21 | Pages | 8087-98 |
| PubMed ID | 16908544 | Mgi Jnum | J:114652 |
| Mgi Id | MGI:3689666 | Doi | 10.1128/MCB.02410-05 |
| Citation | Demarco IA, et al. (2006) Dynamic interactions between Pit-1 and C/EBPalpha in the pituitary cell nucleus. Mol Cell Biol 26(21):8087-98 |
| abstractText | The homeodomain (HD) transcription factors are a structurally conserved family of proteins that, through networks of interactions with other nuclear proteins, control patterns of gene expression during development. For example, the network interactions of the pituitary-specific HD protein Pit-1 control the development of anterior pituitary cells and regulate the expression of the hormone products in the adult cells. Inactivating mutations in Pit-1 disrupt these processes, giving rise to the syndrome of combined pituitary hormone deficiency. Pit-1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to regulate prolactin transcription. Here, we used the combination of biochemical analysis and live-cell microscopy to show that two different point mutations in Pit-1, which disrupted distinct activities, affected the dynamic interactions between Pit-1 and C/EBPalpha in different ways. The results showed that the first alpha-helix of the POU-S domain is critical for the assembly of Pit-1 with C/EBPalpha, and they showed that DNA-binding activity conferred by the HD is critical for the final intranuclear positioning of the metastable complex. This likely reflects more general mechanisms that govern cell-type-specific transcriptional control, and the results from the analysis of the point mutations could indicate an important link between the mislocalization of transcriptional complexes and disease processes. |
