This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Catalano, R. D. Articles by Hillhouse, E. W. Search for Related Content PubMed PubMed Citation Articles by Catalano, R. D. Articles by Hillhouse, E. W.

Regulation of Corticotropin-Releasing Hormone Type 2 Receptors by Multiple Promoters and Alternative Splicing: Identification of Multiple Splice Variants

Department of Pathology (R.D.C.), University of Cambridge, Cambridge CB2 1QP, United Kingdom; Department of Biological Sciences (T.K., J.C., A.E.), University of Warwick, Coventry CV4 7AL, United Kingdom; and The Medical School (E.W.H.), University of Leeds, Leeds LS2 9NL, United Kingdom

Address all correspondence and requests for reprints to: Edward W. Hillhouse, Office of the Dean, Worsley Building, The Medical School, The University of Leeds, Leeds, LS2 9NL, United Kingdom. E-mail: e.w.hillhouse{at}leeds.ac.uk.

We demonstrate that multiple promoters and alternate splicing regulate expression of the human CRH receptor type 2 (CRHR2) gene. We show that flanking regions to the first exons drive promoter activity in both endogenously and nonendogenously expressing cell lines. Putative promoter elements have been identified that are conserved between species, including the comparison of CRHR2 in nonhuman primates that was previously known only in humans, which may be responsible for subtype tissue specific regulation. We have identified novel transcripts produced by alternate splicing of the first exon of CRHR2_ß (ß1a) with various combinations of the 5' exons including a novel exon (ß1c) spliced to the common exons. The 5' structure of the gene permits many other combinations of alternate splicing that may arise as part of a regulatory mechanism controlling functional receptor expression. The 5'-untranslated region of the first exons has been extended; and 3' acceptor sites identified within the 5' untranslated region of CRHR2 and CRHR2 are used during alternate splicing of CRHR2_ß upstream exons. This has important implications because various reports on the expression of CRHR2 and CRHR2 have been unable to discriminate between the functional receptor and CRHR2_ß alternate splice variants. Only the described sequences upstream of the 3' splice site are unique to CRHR2 and CRHR2.

This article has been cited by other articles:

				A. C Moss, P. Anton, T. Savidge, P. Newman, A. S Cheifetz, J. Gay, S. Paraschos, M. W. Winter, M. P Moyer, K. Karalis, et al. Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2{alpha} Gut, September 1, 2007; 56(9): 1210 - 1217. [Abstract] [Full Text] [PDF]

				S. V. Wu, P.-q. Yuan, L. Wang, Y. L. Peng, C.-Y. Chen, and Y. Tache Identification and Characterization of Multiple Corticotropin-Releasing Factor Type 2 Receptor Isoforms in the Rat Esophagus Endocrinology, April 1, 2007; 148(4): 1675 - 1687. [Abstract] [Full Text] [PDF]

				E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology Endocr. Rev., May 1, 2006; 27(3): 260 - 286. [Abstract] [Full Text] [PDF]

				J. Xu, J. D. Hennebold, and R. L. Stouffer Dynamic Expression and Regulation of the Corticotropin-Releasing Hormone/Urocortin-Receptor-Binding Protein System in the Primate Ovary during the Menstrual Cycle J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1544 - 1553. [Abstract] [Full Text] [PDF]

				J. Xu, R.L. Stouffer, R.P. Searles, and J.D. Hennebold Discovery of LH-regulated genes in the primate corpus luteum Mol. Hum. Reprod., March 1, 2005; 11(3): 151 - 159. [Abstract] [Full Text] [PDF]

				A. Chen, M. Perrin, B. Brar, C. Li, P. Jamieson, M. DiGruccio, K. Lewis, and W. Vale Mouse Corticotropin-Releasing Factor Receptor Type 2{alpha} Gene: Isolation, Distribution, Pharmacological Characterization and Regulation by Stress and Glucocorticoids Mol. Endocrinol., February 1, 2005; 19(2): 441 - 458. [Abstract] [Full Text] [PDF]

				S. A. Nanda, P. H. Roseboom, G. A. Nash, J. M. Speers, and N. H. Kalin Characterization of the Human Corticotropin-Releasing Factor2(a) Receptor Promoter: Regulation by Glucocorticoids and the Cyclic Adenosine 5'-Monophosphate Pathway Endocrinology, December 1, 2004; 145(12): 5605 - 5615. [Abstract] [Full Text] [PDF]

				K. L. Parham, S. Zervou, E. Karteris, R. D. Catalano, R. W. Old, and E. W. Hillhouse Promoter Analysis of Human Corticotropin-Releasing Factor (CRF) Type 1 Receptor and Regulation by CRF and Urocortin Endocrinology, August 1, 2004; 145(8): 3971 - 3983. [Abstract] [Full Text] [PDF]

				A. Slominski, A. Pisarchik, D. J. Tobin, J. E. Mazurkiewicz, and J. Wortsman Differential Expression of a Cutaneous Corticotropin-Releasing Hormone System Endocrinology, February 1, 2004; 145(2): 941 - 950. [Abstract] [Full Text] [PDF]