Histone acetylase

Co regulators of transcription — histone acetylases modulate chromatin structure 461... 

Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102 463-473... 

Histone acetylases (fevor gene expression) and deacefylases (favor inactive chromatin)... 

Recruit chromatin-modifying proteins such as histone acetylases or deacetylases... 

In the resting state, the lysine residues in the N-terminal tail of the histones (see p. 238) are not acetylated. In this state, which can be produced by histone deacetylases [1], the nucleosomes are stable. It is only the interaction of activator and regulator proteins with their control elements that allows the binding of coactivator complexes that have histone acetylase activity [2]. They acetylate the histone tails and thereby loosen the nu-cleosome structure suf ciently for the basal transcription complex to form. 

Kouzarides, T. (1999) Histone acetylases and deacetylases in cell proliferation. Current Opinion in Genetics d. Development, 9, 40-48. 

The TAFs fulfill numerous functions (Review Burley and Boeder, 1996 Struhl and Moqtaderi, 1998). On the one hand they are ascribed a structure promoting function. Some of the TAFs display a high degree of homology to the histones H2A, H3 and H4, and it is speculated that they help to create a nucleosome-like structure at the promotor. Furthermore, the TAFs are targets for protein-protein interactions with transcriptional activators. TAFs also posses enzymatic activity. TAF11250 has both a histone acetylase activity and a protein kinase activity. While the former presumable plays a role in the reorganization of the nucleosome, the latter can lead to phosphorylation of TFIIF. 

The TAFs are components of TFIID (see table 1.1) and are required for a regulated transcription (review Verriijzer and Tijan 1996, Bmley and Roeder, 1996 ). Thus, the stimulation of transcription by the transcriptional activators Spl and NTF-1 depends upon the presence of specific TAFs in the TFllD complex. The TAFs mediate interactions between the transcriptional activators and the TFllD complex in many cases direct protein-protein interactions could be demonstrated between the activators and TAFs. Some of the TAFs possess additional enzymatic activities which allow them to participate in the regulation of transcription. By this token, the histone acetylase and protein kinase activity of TAFn250 is ascribed a regulatory function in the remodeling of chromatin and in the control of the activity of the basal transcription factors. 

Overall, the physiological function of individual TAFs is still incompletely imder-stood. The situation is complicated by the fact that a subset of the TAFs, including the histone-like TAFs, have been identified as components of a large histone acetylase complex, termed SAGA in yeast and PCAF (p300/CBP associated factor) in humans (see 1.4.6). 

Among the general cofactors are also included proteins with histone acetylase activity (HAT) or histone deacetylase activity (HDAC). The acetylation/deacetylation of histones plays a significant role in transcription regulation of chromatin-coated DNA. 

Examples for coactivators with histone acetylase activity are the CBP protein, the p300 protein and the GCN5 protein (see 1.4.6). 

Hassig, C.A. and Schreiber, S.L. Nuclear histone acetylases and deacetylases and transcriptional regulation HATs off to HDACs (1997) Curr Opin Chem Biol. 1, 300-308. 

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).

Structure of chromatin which promotes transcription. A large protein complex takes part in this remodeling. Some of the proteins in the complex, like the CBP/p300 protein (see also 1.4.6), possess histone acetylase activity. The activated, DNA-boimd receptor possibly recruits a histone acetylase to the chromatin. It can thus create the conditions necessary for the formation of a transcription initiation complex by this histone modification. 

Activation is a complex process in which various types of co-activators participate. Among these are foimd histone acetylases (see 1.4.6). 

The interaction of glucocorticoid receptors with GREs or other transcription factors is facilitated or inhibited by several families of proteins called steroid receptor coregulators, divided into coactivators and corepressors. The coregulators do this by serving as bridges between the receptors and other nuclear proteins and by expressing enzymatic activities such as histone acetylase or deacetylase, which alter the... 

Table 9.6 Actin, histone acetylase, histone deacetylase, cell division and tubulin...

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