| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 4, 2001
Accepted on October 28, 2002
) REQUIRED FOR PRL GENE TRANSCRIPTION
1 Departments of Medicine and Cell Biology, University of Virginia Health System, Charlottesville, VA, 22908-0578; Metabolic Research Unit, Box 0540, University of California, San Francisco, California, 94143-0540
* To whom correspondence should be addressed. E-mail: rnd2v{at}virginia.edu.
The pituitary-specific homeodomain protein Pit-1 cooperates with other transcription factors, including CCAAT/enhancer binding protein alpha (C/EBP
), in the regulation of pituitary lactotrope gene transcription. Here, we correlate cooperative activation of PRL (PRL) gene transcription by Pit-1 and C/EBP with changes in the subnuclear localization of these factors in living pituitary cells. Transiently expressed C/EBP induced PRL gene transcription in pituitary GHFT1-5 cells, whereas the co-expression of Pit-1 and C/EBP in HeLa cells demonstrated their cooperativity at the PRL promoter. Individually expressed Pit-1 or C/EBP, fused to color variants of fluorescent proteins (FPs), occupied different subnuclear compartments in living pituitary cells. When co-expressed, Pit-1 recruited C/EBP 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/EBP. A point mutation in the Pit-1 homeodomain associated with the syndrome of combined pituitary hormone deficiency in humans also failed to recruit C/EBP. This Pit-1 mutant functioned as a dominant inhibitor of PRL gene transcription, and instead of recruiting C/EBP, was itself recruited by C/EBP to centromeric heterochromatin. Together our results suggest that the intranuclear positioning of these factors determines whether they activate or silence PRL promoter activity.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  G. N. Corry, M. J. Hendzel, and D. A. Underhill Subnuclear localization and mobility are key indicators of PAX3 dysfunction in Waardenburg syndrome Hum. Mol. Genet., June 15, 2008; 17(12): 1825 - 1837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, B. Wu, J. Szary, E. M. Kofoed, and F. Schaufele Functional Sequestration of Transcription Factor Activity by Repetitive DNA J. Biol. Chem., July 20, 2007; 282(29): 20868 - 20876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Pellegrini, C. Roche, M.-H. Quentien, M. Ferrand, G. Gunz, S. Thirion, C. Bagnis, A. Enjalbert, and J.-L. Franc Involvement of the Pituitary-Specific Transcription Factor Pit-1 in Somatolactotrope Cell Growth and Death: An Approach Using Dominant-Negative Pit-1 Mutants Mol. Endocrinol., December 1, 2006; 20(12): 3212 - 3227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Demarco, T. C. Voss, C. F. Booker, and R. N. Day Dynamic Interactions between Pit-1 and C/EBP{alpha} in the Pituitary Cell Nucleus Mol. Cell. Biol., November 1, 2006; 26(21): 8087 - 8098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Voss, I. A. Demarco, C. F. Booker, and R. N. Day Functional interactions with Pit-1 reorganize co-repressor complexes in the living cell nucleus J. Cell Sci., August 1, 2005; 118(15): 3277 - 3288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Schaufele, X. Wang, X. Liu, and R. N. Day Conformation of CCAAT/Enhancer-binding Protein alpha Dimers Varies with Intranuclear Location in Living Cells J. Biol. Chem., March 14, 2003; 278(12): 10578 - 10587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Day, T. C. Voss, J. F. Enwright III, C. F. Booker, A. Periasamy, and F. Schaufele Imaging the Localized Protein Interactions Between Pit-1 and the CCAAT/Enhancer Binding Protein {alpha} in the Living Pituitary Cell Nucleus Mol. Endocrinol., March 1, 2003; 17(3): 333 - 345. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
