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Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation

Oncogene volume 26, pages 5341–5357 (2007)Cite this article

Abstract

Transcription in eukaryotes is a tightly regulated, multistep process. Gene-specific transcriptional activators, several different co-activators and general transcription factors are necessary to access specific loci to allow precise initiation of RNA polymerase II transcription. As the dense chromatin folding of the genome does not allow the access of these sites by the huge multiprotein transcription machinery, remodelling is required to loosen up the chromatin structure for successful transcription initiation. In the present review, we summarize the recent evolution of our understanding of the function of two histone acetyl transferases (ATs) from metazoan organisms: GCN5 and PCAF. Their overall structure and the multiprotein complexes in which they are carrying out their activities are discussed. Metazoan GCN5 and PCAF are subunits of at least two types of multiprotein complexes, one having a molecular weight of 2 MDa (SPT3-TAF9-GCN5 acetyl transferase/TATA binding protein (TBP)–free–TAF complex/PCAF complexes) and a second type with about a size of 700 kDa (ATAC complex). These complexes possess global histone acetylation activity and locus-specific co-activator functions together with AT activity on non-histone substrates. Thus, their biological functions cover a wide range of tasks and render them indispensable for the normal function of cells. That deregulation of the global and/or specific AT activities of these complexes leads to the cancerous transformation of the cells highlights their importance in cellular processes. The possible effects of GCN5 and PCAF in tumorigenesis are also discussed.

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Acknowledgements

We apologize to colleagues whose work could only be cited indirectly in this review, and are grateful to P Schultz for help in preparing Figure 2, ME Torres Padilla, A Krebs and M Sumner for critically reading the manuscript. ZN was funded by a EU Marie Curie RTN Fellowship (HPRN-CT 00504228). This work was supported by grants from INSERM, CNRS, Université Louis Pasteur de Strasbourg, the Fond National de la Science ACI, the Agence Nationale de la Recherche, EU STREP (LSHG-CT-2004-502950) and EU RTN (HPRN-CT 00504228).

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Nagy, Z., Tora, L. Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene 26, 5341–5357 (2007). https://doi.org/10.1038/sj.onc.1210604

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