Regulation of Major Histocompatibility Complex Class I Gene Expression in Thyroid Cells
The major histocompatibility complex (MHC) class I gene cAMP response element (CRE)-like site, −107 to −100 base pairs, is a critical component of a previously unrecognized silencer, −127 to −90 bp, important for thyrotropin (TSH)/cAMP-mediated repression in thyrocytes. TSH/cAMP induced-silencer act...
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Published in | The Journal of biological chemistry Vol. 272; no. 32; pp. 20096 - 20107 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
08.08.1997
American Society for Biochemistry and Molecular Biology |
Online Access | Get full text |
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Summary: | The major histocompatibility complex (MHC) class I gene cAMP response element (CRE)-like site, −107 to −100 base pairs, is a critical component of a previously unrecognized silencer, −127 to −90 bp, important for thyrotropin (TSH)/cAMP-mediated repression in thyrocytes. TSH/cAMP induced-silencer activity is associated with the formation of novel complexes with the 38-base pair silencer, whose appearance requires the CRE and involves ubiquitous and thyroid-specific proteins as follows: the CRE-binding protein, a Y-box protein termed thyrotropin receptor (TSHR) suppressor element protein-1 (TSEP-1); thyroid transcription factor-1 (TTF-1); and Pax-8. TTF-1 is an enhancer of class I promoter activity; Pax-8 and TSEP-1 are suppressors. TSH/cAMP decreases TTF-1 complex formation with the silencer, thereby decreasing maximal class I expression; TSH/cAMP enhance TSEP-1 and Pax-8 complex formation in association with their repressive actions. Oligonucleotides that bind TSEP-1, not Pax-8, prevent formation of the TSH/cAMP-induced complexes associated with TSH-induced class I suppression, i.e. TSEP-1 appears to be the dominant repressor factor associated with TSH/cAMP-decreased class I activity and formation of the novel complexes. TSEP-1, TTF-1, and/or Pax-8 are involved in TSH/cAMP-induced negative regulation of the TSH receptor gene in thyrocytes, suppression of MHC class II, and up-regulation of thyroglobulin. TSH/cAMP coordinate regulation of common transcription factors may, therefore, be the basis for self-tolerance and the absence of autoimmunity in the face of TSHR-mediated increases in gene products that are important for thyroid growth and function but are able to act as autoantigens. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.272.32.20096 |