RGD Reference Report - A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription. - Rat Genome Database

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A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription.

Authors: Enwright JF, 3RD  Kawecki-Crook, MA  Voss, TC  Schaufele, F  Day, RN 
Citation: Enwright JF 3rd, etal., Mol Endocrinol 2003 Feb;17(2):209-22.
RGD ID: 1304355
Pubmed: PMID:12554749   (View Abstract at PubMed)
PMCID: PMC2900764   (View Article at PubMed Central)
DOI: DOI:10.1210/me.2001-0222   (Journal Full-text)

The pituitary-specific homeodomain protein Pit-1 cooperates with other transcription factors, including CCAAT/enhancer binding protein alpha (C/EBPalpha), in the regulation of pituitary lactotrope gene transcription. Here, we correlate cooperative activation of prolactin (PRL) gene transcription by Pit-1 and C/EBPalpha with changes in the subnuclear localization of these factors in living pituitary cells. Transiently expressed C/EBPalpha induced PRL gene transcription in pituitary GHFT1-5 cells, whereas the coexpression of Pit-1 and C/EBPalpha in HeLa cells demonstrated their cooperativity at the PRL promoter. Individually expressed Pit-1 or C/EBPalpha, fused to color variants of fluorescent proteins, occupied different subnuclear compartments in living pituitary cells. When coexpressed, Pit-1 recruited C/EBPalpha from regions of transcriptionally quiescent centromeric heterochromatin to the nuclear regions occupied by Pit-1. The homeodomain region of Pit-1 was necessary for the recruitment of C/EBPalpha. A point mutation in the Pit-1 homeodomain associated with the syndrome of combined pituitary hormone deficiency in humans also failed to recruit C/EBPalpha. This Pit-1 mutant functioned as a dominant inhibitor of PRL gene transcription and, instead of recruiting C/EBPalpha, was itself recruited by C/EBPalpha to centromeric heterochromatin. Together our results suggest that the intranuclear positioning of these factors determines whether they activate or silence PRL promoter activity.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CebpaRatregulation of DNA-templated transcription  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CebpaRattranscription regulator complex  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CebpaRatDNA binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cebpa  (CCAAT/enhancer binding protein alpha)


Additional Information