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Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 beta.

Authors: Sporici, RA  Hodskins, JS  Locasto, DM  Meszaros, LB  Ferry, AL  Weidner, AM  Rinehart, CA  Bailey, JC  Mains, IM  Diamond, SE 
Citation: Sporici RA, etal., J Mol Endocrinol. 2005 Oct;35(2):317-31.
Pubmed: (View Article at PubMed) PMID:16216912
DOI: Full-text: DOI:10.1677/jme.1.01678

The POU-homeodomain transcription factor Pit-1 is required for the differentiation of the anterior pituitary cells and the expression of their hormone products. Pit-1beta, an alternate splicing isoform, has diametrically different outcomes when it is expressed in different cell types. Pit-1beta acts as a transcriptional repressor of prolactin (PRL) and growth hormone genes in pituitary cells, and as a transcriptional activator in non-pituitary cells. In order to explore these differences, we: (1) identified the transcriptional cofactors necessary for reconstitution of repression in non-pituitary cells; (2) tested the effect of the beta-domain on heterodimerization with Pit-1 and physical interaction with the co-activator CREB binding protein (CBP); and (3) determined the beta-domain sidechain chemistry requirements for repression. Co-expression of both Pit-1 isoforms reconstituted the repression of the PRL promoter in non-pituitary cells. The beta-domain allowed heterodimerization with Pit-1 but blocked physical interaction with CBP, and specific chemical properties of the beta-domain beyond hydrophobicity were dispensable. These data strongly suggest that Pit-1beta represses hormone gene expression by heterodimerizing with Pit-1 and interfering with the assembly of the Pit-1-CBP complex required for PRL promoter activity in pituitary cells.


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CRRD Object Information
CRRD ID: 1601440
Created: 2007-04-20
Species: All species
Last Modified: 2007-04-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.