This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kirshner, S. Articles by Singer, D. S. Search for Related Content PubMed PubMed Citation Articles by Kirshner, S. Articles by Singer, D. S.

Major Histocompatibility Class I Gene Transcription in Thyrocytes: A Series of Interacting Regulatory DNA Sequence Elements Mediate Thyrotropin/Cyclic Adenosine 3',5'-Monophosphate Repression

Experimental Immunology Branch (S.K., L.P., J.B., D.S.S.) National Cancer Institute, and Cell Regulation Section Metabolic Diseases Branch (M.S., L.D.K.) National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland 20892

In response to TSH, thyroid cells decrease major histocompatibility (MHC) class I expression and transcription, providing an excellent model for studying the dynamic modulation of transcription of MHC class I genes. Here we show that protein kinase A (PKA), a downstream effector of the TSH/cAMP pathway, reproduces the effects of TSH in repressing class I transcription. PKA/cAMP-mediated repression of transcription involves multiple interacting upstream response elements in the class I promoter: an element extending from -127 to -90 bp containing a CRE-like core, and at least two elements within an upstream 30-bp segment (-160 to -130 bp), which overlaps with the interferon regulatory element. ICER (inducible cAMP early response), a transcriptional repressor induced by TSH/cAMP can decrease class I promoter activity when introduced into FRTL-5 thyroid cells in the absence of TSH/cAMP. ICER binds to both the CRE-like element and the upstream 30-bp segment, generating a novel TSH-induced ternary complex. The present studies led to the proposal that TSH-mediated repression of class I transcription is the result of integrating signals from transcription factors through the higher order interactions of multiple regulatory elements.

This article has been cited by other articles:

				A. Grassadonia, N. Tinari, B. Fiorentino, M. Nakazato, H.-K. Chung, C. Giuliani, G. Napolitano, S. Iacobelli, T. K. Howcroft, D. S. Singer, et al. Upstream Stimulatory Factor Regulates Constitutive Expression and Hormonal Suppression of the 90K (Mac-2BP) Protein Endocrinology, July 1, 2007; 148(7): 3507 - 3517. [Abstract] [Full Text] [PDF]

				T. K. Howcroft, J. D. Weissman, A. Gegonne, and D. S. Singer A T Lymphocyte-Specific Transcription Complex Containing RUNX1 Activates MHC Class I Expression J. Immunol., February 15, 2005; 174(4): 2106 - 2115. [Abstract] [Full Text] [PDF]

				J.-C. Goffard, L. Jin, H. Mircescu, P. Van Hummelen, C. Ledent, J.-E. Dumont, and B. Corvilain Gene Expression Profile in Thyroid of Transgenic Mice Overexpressing the Adenosine Receptor 2a Mol. Endocrinol., January 1, 2004; 18(1): 194 - 213. [Abstract] [Full Text] [PDF]

				H. Kim, J. M. Suh, E. S. Hwang, D. W. Kim, H. K. Chung, J. H. Song, J. H. Hwang, K. C. Park, H. K. Ro, E.-K. Jo, et al. Thyrotropin-Mediated Repression of Class II Trans-Activator Expression in Thyroid Cells: Involvement of STAT3 and Suppressor of Cytokine Signaling J. Immunol., July 15, 2003; 171(2): 616 - 627. [Abstract] [Full Text] [PDF]