A 10-Amino-Acid Sequence in the N-Terminal A/B Domain of Thyroid Hormone Receptor α Is Essential for Transcriptional Activation and Interaction with the General Transcription Factor TFIIB

Abstract

Transcription of eukaryotic protein-encoding genes by RNA polymerase II is modulated by two distinct classes of transcription factors. The first class comprises general transcription factors which are necessary for accurate initiation of transcription. These factors include TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIG/J, and TFIIH (11, 82). TFIID is a multiprotein complex consisting of TATA-binding protein (TBP) complexed with a number of TBP-associated factors (73). The binding of TFIID is thought to be the first step in transcriptional initiation (11, 82). The subsequent binding of TFIIB is thought to be involved in bringing RNA polymerase II to the complex through the association of TFIIF (34, 37). This leads to the recruitment of TFIIE and TFIIH and possibly other factors, which ultimately results in the initiation of transcription (11,75,82).The magnitude of transcriptional activity is greatly affected by the second class of transcription factors that generally bind to distal control DNA elements (52). These sequence-specific factors act to either promote or inhibit the formation of an active transcriptional initiation complex. Recent in vitro transcription studies suggest that the entry of TFIIB may be rate limiting for transcriptional initiation and that several transcriptional activators act to recruit or stabilize the interaction of TFIIB with the initiation complex (14, 62). TFIIB contains a potential N-terminal zinc finger structure (amino acids 14 to 36) that may be important for interaction with RNA polymerase II and TFIIF (34), a more C-terminal amphipathic ␣ helix (amino acids 184 to 201), and two imperfect repeats (amino acids 124 to 201 and 218 to 294) (34,37,62) (Fig. 1A). The amphipathic ␣ helix appears to be important for interaction with TBP (34, 37) and several transcriptional activators such as the herpes simplex virus VP16 protein (62).Members of the steroid/thyroid hormone receptor gene family are sequence-specific DNA-binding proteins that play important roles in gene regulation. The steroid hormone receptor subfamily includes the receptors which mediate the effects of glucocorticoids, progestins, mineralocorticoids, androgens, and estrogens (12, 16). The thyroid/retinoid receptor subfamily (16, 21) includes receptors that mediate the effects of thyroid hormone (3,5,3Ј-triiodo-L-thyronine [T3]), all-trans retinoic acid, 9-cis retinoic acid, and 1,25-dihydroxyvitamin D 3 as well as several orphan receptors (e.g., COUP-TF and c-ErbA␣2) whose ligands, if any, are unknown (26,27,44). Steroid/thyroid receptors bind to specific DNA sequences known as hormone response elements (HREs) and mediate ligand-dependent ac-

Transcriptional Activation by Peroxisome Proliferator-activated Receptor γ Is Inhibited by Phosphorylation at a Consensus Mitogen-activated Protein Kinase Site

“…A third possibility is that phosphorylation inhibits the activity of PPAR␥ by altering receptor interaction with other transcription intermediary proteins. For example, an interaction between the A/B domain of thyroid hormone receptors TR␤2 and TR␣1 and TFIIB, which might influence transcription by altering preinitiation complex formation or stability, has recently been described (40,41). This raises the possibility of analogous interactions between basal transcription factors and the A/B region of PPAR␥ that are phosphorylation-sensitive.…”

Hepatic regulation of fatty acid synthase by insulin and T3: evidence for T3genomic and nongenomic actions

“…involve FAS basal repression, as previously described for many other genes positively regulated by T 3 (97). In this case, the TR/RXR complex would interact with TFIIB (4,38), interfering with the formation of the transcription preinitializing complex. This basal repression is also maintained through the association of TFIIB with corepressors (40,54).…”

Biological activities of thyroid hormone receptors

“…Its action appears to be mediated through interaction with components of the basal transcription machinery, specifically with transcription factor IIB (TFIIB) (48,49). Deletion of amino acids 21 to 30 of chicken TRa decreases the activating capacity by 10-to 20-fold (50). Though this region does not contain an intrinsic activation domain, it is important for interaction with TFIIB.…”