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* Steroid hormones are too hydrophobic to readily dissolve in blood. Therefore, they travel on specific carrier proteins from point of release to their target tissues. In the target tissue, the hormone passes through the plasma membrane by simple diffusion and binds to its specific receptor protein in the cytoplasm (as shown here) or in the nucleus (see retinoic acid receptor [RAR] below). * * Near the initiation site A little far away SP1 stimulates transcription in presence of TAFII110 GC boxes bound by DNA binding protein SP1 SP1 recruits TFIID by binding TAFII110 Partially reconstituted complex (TBP and 3 TAFs) in addition to other GTFs, Pol II leads to high levels of transcription SV40 early promoter Near Mediator complex is targeted by an activator Mediator is a stable complex containing several proteins (20-50) Mediator binds to the RNA pol II and transcription factors (activators or repressors) and ‘mediates’ the regulatory signals to pol II (中介复合体) Far What is the mechanism of activation? Two models: Tethering holoenzyme (recruitment) Activating holoenzyme (allosteric) (interaction activation) ?? In favor of recruitment model (勾引模型) tat protein of HIV can stimulate transcription initiation without binding DNA at all The activating domain of the tat protein can stimulate transcription if it is tethered in the vicinity of promoter by binding to the RNA product (tar sequence) of a previous round of transcription. tar tat DNA-binding domain is to bring the activation domain into the vicinity of the startpoint. And activation is independent of the means of tethering. we can think of DNA-binding (or RNA-binding in the case of tat) domain as providing a tethering function, whose main purpose is to ensure that the activation domain is in the vicinity of the initiation complex. The notion of tethering is a more general idea that initiation requires a high concentration of transcription factors in the vicinity of the promoter. This may b
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