Dynamic interactions between Pit-1 and C/EBPα in the pituitary cell nucleus

Ignacio A. Demarco, Ty C. Voss, Cynthia F. Booker, Richard N. Day

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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/EBPα) 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/EBPα in different ways. The results showed that the first α-helix of the POU-S domain is critical for the assembly of Pit-1 with C/EBPα, 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.

Original languageEnglish (US)
Pages (from-to)8087-8098
Number of pages12
JournalMolecular and cellular biology
Volume26
Issue number21
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Dynamic interactions between Pit-1 and C/EBPα in the pituitary cell nucleus'. Together they form a unique fingerprint.

  • Cite this