The N-terminal region (A/B) of rat thyroid hormone receptors alpha 1, beta 1, but not beta 2 contains a strong thyroid hormone-dependent transactivation function.
In this study we have investigated the role of the N-terminal region of thyroid hormone receptors (TRs) in thyroid hormone (TH)-dependent transactivation of a thymidine kinase promoter containing TH response elements composed either of a direct repeat or an inverted palindrome. Comparison of rat TR beta 1 with TR beta 2 provides an excellent model since they share identical sequences except for their N termini. Our results show that TR beta 2 is an inefficient TH-dependent transcriptional activator. The degree of transactivation corresponds to that observed for the mutant TR delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2. Thus, TH-dependent activation appears to be associated with two separate domains. The more important region, however, is embedded in the N-terminal domain. Furthermore, the transactivating property of TR alpha 1 was also localized to the N-terminal domain between amino acids 19 and 30. Using a coimmunoprecipitation assay, we show that the differential interaction of the N terminus of TR beta 1 and TR beta 2 with transcription factor IIB correlates with the TR beta 1 activation function. Hence, our results underscore the importance of the N-terminal region of TRs in TH-dependent transactivation and suggest that a transactivating signal is transmitted to the general transcriptional machinery via a direct interaction of the receptor N-terminal region with transcription factor IIB.
Tomura
H
H
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1766, USA.
Lazar
J
J
Phyillaier
M
M
Nikodem
V M
VM
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D008291:Malate Dehydrogenase / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics; D011233:Precipitin Tests; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000502:physiology*; D013963:Thyroid Hormones / Q000502:physiology*; D015533:Transcriptional Activation
D017931:DNA Primers; D004676:Myelin Basic Protein; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating)