Major histocompatibility class I gene transcription in thyrocytes: A series of interacting regulatory DNA sequence elements mediate thyrotropin/cyclic adenosine 3 ',5 '-monophosphate repression

in response to TSH, thyroid cells decrease major histocompatibility (MHC) c lass I expression and transcription, providing an excellent model for study ing the dynamic modulation of transcription of MHC class I genes. Here we s how that protein kinase A (PKA), a downstream effector of the TSH/cAMP path way, reproduces the effects of TSH in repressing class I transcription. PKA /cAMP-mediated repression of transcription involves multiple interacting up stream 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 withi n an upstream 30-bp segment (-160 to -130 bp), which overlaps with the inte rferon regulatory element. ICER (inducible cAMP early response), a transcri ptional repressor induced by TSH/cAMP can decrease class I promoter activit y when introduced into FRTL-5 thyroid cells in the absence of TSH/cAMP. ICE R binds to both the CRE-like element and the upstream 30-bp segment, genera ting a novel TSH-induced ternary complex. The present studies led to the pr oposal 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.