RNA polymerase II holoenzyme

WUson CJ, Chao DM, Imbalzano AN, Schnitzler GR, Kingston RE, Young RA (1996) RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell 84(2) 235-244... 

Studies in yeast have shown that pre-formed RNA polymerase II holoenzyme complexes can be foimd in the cell associated with some of the general transcription factors. 

Fig. 1.34 Activators and coactivators of transcription intiation. The figure shows the function of three groups of proteins that function as coactivators. The general cofactors mediate the interactions between the specific transcription activators and the TFIID complex as well as with various forms of the RNA polymerase II holoenzyme. The TAFs are components of the TFIID complex and serve as contact points for specific transcription activators. The mediators are components of various forms of holoenzymes of RNA polymerase II. SRB proteins belong to the class of mediators, which, among other things, interacts with the CTD of RNA polymerase. The simphfied diagram does not show the interactions with chromatin.

Fig. 4.10. Principle of signal transduction by steroid hormone receptors. The steroid hormone receptors in the cytosol are found in the form of an inactive complex with the heat shock proteins Hsp90 and Hsp56 and with protein p23. The binding of the hormone activates the receptor so that it can be transported into the nucleus where it binds to its cognate HRE. It remains unclear in which form the receptor is transported into the nucleus, and to which extent the associated proteins are involved in the transport. One mechanism of activation of transcription initiation involves activation of a histone acetylase and remodehng of chromatin. Furthermore, the receptors interact directly or indirectly with components of the RNA polymerase II holoenzyme (e.g. SUGl).

Due to the complex structure of the initiation complex it remains imclear which interactions are responsible for the first mechanism. The coupling between the transactivat-ing domain and the initiation complex can be direct or indirect. There is evidence which indicates that proteins with co-activator function mediate the interaction between HRE-bound receptors and the transcription initiation apparatus. One such protein is RIP-140, which mediates the transcription activation of the estrogen receptor. The AF2 domain can also directly contact the transcriptional apparatus. One component of the RNA polymerase II holoenzyme, the SUGl protein, has been identified as a binding partner for the AF2 domain. The SUGl protein has the function of a co-acti-vator in transcription initiation and is considered a mediator (see 1.4.3.2). 

Holoenzyme forms of RNA polymerase II have general transcription factors associated. TFIIB, TFIIE, TFIIF and TFIIH have been identified as components of the RNA polymerase II holoenzyme of yeast. 

The yeast holoenzyme contains further proteins, known as mediators or SRB proteins (SRB, suppressor of RNA polymerase B). The mediators function as coactivators (see Section 1.4.4.2) and appear to integrate signals from transcriptional activators at promotors. A complete structural characterization of the holoenzyme has proven to be difficult, because some of the proteins accessory to the core enzyme are not permanently and are often only loosely associated with the core of RNA polymerase II. Clearly different forms of the RNA polymerase II holoenzyme exist in the living cell, each of slightly different composition and function. 

Transcriptional activators or repressors can intervene as regulators at various steps in the initiation of transcription. They can interact with components of TFIID, as well as with components of the RNA polymerase II holoenzyme to stimulate transcription. Furthermore, contacts to chromatin proteins are formed to change the structure of chromatin during transcription initiation and ongoing elongation. Regulated transcription and chromatin modification generally requires the aid of further protein components, which are commonly termed coactivators (see Section 1.4.4.2). 

Many general repressors function via components of the basal transcription machinery, with the TATA box-binding protein TBP as the major target. Repressors like NC2 are known that bind to the TBP on the promotor and can prevent RNA polymerase II holoenzyme from assembling into the initiation complex. In this way, a general repression of class II genes can be achieved. 

Greenblatt, J. (1997). RNA polymerase II holoenzyme and transcriptional regulation. Curr. Opin. Cell. Biol. 9(3), 310-319. 

Ossipow, V., Iassan, J.-P., Nigg, E. A., and Schibler, U. (1995). A mammalian RNA polymerase II holoenzyme containing all components required for promoter-specific transcription initiation. Cell 83, 137-146. 

Gaudreau L, Adam MA, Ptashne M. Activation of transcription in vitro by recruitment of the yeast RNA polymerase II holoenzyme. Mol Cell 1998 1 913 916. 

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