Molecular Endocrinology, Vol 6, 581-588, Copyright © 1992 by Endocrine Society

ARTICLES

Analysis of functional cooperativity between individual transcription- stimulating elements in the proximal region of the rat prolactin gene

MC d'Emden, Y Okimura and RA Maurer
Department of Physiology and Biophysics, University of Iowa, Iowa City 52242.

The proximal region of the rat PRL gene contains at least five transcription-stimulating elements that are located within a 170- basepair region up-stream of the TATA box. These cis-acting elements include four binding sites for the pituitary-specific transcription factor Pit-1 as well as another site for an unidentified factor. In this study interactions between different DNA elements have been examined through the construction of PRL-luciferase fusion genes containing mutations that disrupt various combinations of the individual DNA elements. In general, the disruption of multiple factor- binding sites had a much more than additive effect on expression of the luciferase constructs. Interestingly, comparison of the effects of disrupting pairs of binding sites demonstrated substantial differences in the effects of different combinations of mutations, suggesting that cooperative interactions may reflect specific interactions. Mutations that disrupted all five cis-elements of the PRL proximal region essentially abolished transcription from the proximal promoter. This finding suggests that there are no other DNA elements within the proximal 200 basepairs of the PRL gene that can independently stimulate transcription. Although there is strong functional cooperativity between different cis-elements in the PRL gene, DNase footprint studies failed to detect cooperative binding between different Pit-1 elements. Overall, the findings demonstrate that the normal transcription of the PRL gene involves strong cooperative interactions between individual DNA elements in the proximal region.

This article has been cited by other articles:

				P. W. Howard, S. F. Jue, and R. A. Maurer Expression of the Synaptotagmin I Gene Is Enhanced by Binding of the Pituitary-Specific Transcription Factor, POU1F1 Mol. Endocrinol., October 1, 2009; 23(10): 1563 - 1571. [Abstract] [Full Text] [PDF]

				P. Kievit, J. D. Lauten, and R. A. Maurer Analysis of the Role of the Mitogen-Activated Protein Kinase in Mediating Cyclic-Adenosine 3',5'-Monophosphate Effects on Prolactin Promoter Activity Mol. Endocrinol., April 1, 2001; 15(4): 614 - 624. [Abstract] [Full Text]

				E. Suh, Z. Wang, G. P. Swain, M. Tenniswood, and P. G. Traber Clusterin gene transcription is activated by caudal-related homeobox genes in intestinal epithelium Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G149 - G156. [Abstract] [Full Text] [PDF]

				Y.-H. Wang and R. A. Maurer A Role for the Mitogen-Activated Protein Kinase in Mediating the Ability of Thyrotropin-Releasing Hormone to Stimulate the Prolactin Promoter Mol. Endocrinol., July 1, 1999; 13(7): 1094 - 1104. [Abstract] [Full Text]

				K. Zanger, L. E. Cohen, K. Hashimoto, S. Radovick, and F. E. Wondisford A Novel Mechanism for Cyclic Adenosine 3',5'-Monophosphate Regulation of Gene Expression by CREB-Binding Protein Mol. Endocrinol., February 1, 1999; 13(2): 268 - 275. [Abstract] [Full Text]

				M. Li, X. Ye, R. N. Woodward, C. Zhu, L. A. Nichols, and L. J. Holland Analysis of the DNA-binding Site for Xenopus Glucocorticoid Receptor Accessory Factor. CRITICAL NUCLEOTIDES FOR BINDING SPECIFICITY IN VITRO AND FOR AMPLIFICATION OF STEROID-INDUCED FIBRINOGEN GENE TRANSCRIPTION J. Biol. Chem., April 17, 1998; 273(16): 9790 - 9796. [Abstract] [Full Text] [PDF]

				L. C. Jones and J. G. Scammell The cAMP-response element mediates induction of secretogranin II by CHX and FSK in GH4C1 cells Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E656 - E664. [Abstract] [Full Text] [PDF]

				R. N. Woodward, M. Li, and L. J. Holland Novel Accessory Factor-Binding Site Required for Glucocorticoid Regulation of the {gamma}-Fibrinogen Subunit Gene from Xenopus laevis Mol. Endocrinol., May 1, 1997; 11(5): 563 - 576. [Abstract] [Full Text]

				K. N. Farrow, N. Manning, F. Schaufele, and A. Gutierrez-Hartmann The c-Jun delta -Domain Inhibits Neuroendocrine Promoter Activity in a DNA Sequence- and Pituitary-specific Manner J. Biol. Chem., July 19, 1996; 271(29): 17139 - 17146. [Abstract] [Full Text] [PDF]

				J. Liang, S. Moye-Rowley, and R. A. Maurer In Vivo Mutational Analysis of the DNA Binding Domain of the Tissue-specific Transcription Factor, Pit-1 J. Biol. Chem., October 27, 1995; 270(43): 25520 - 25525. [Abstract] [Full Text] [PDF]

				P. W. Howard and R. A. Maurer A Composite Ets/Pit-1 Binding Site in the Prolactin Gene Can Mediate Transcriptional Responses to Multiple Signal Transduction Pathways J. Biol. Chem., September 8, 1995; 270(36): 20930 - 20936. [Abstract] [Full Text] [PDF]

				P Sun, H Enslen, P S Myung, and R A Maurer Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes & Dev., November 1, 1994; 8(21): 2527 - 2539. [Abstract] [PDF]