NuA4 histone acetyltransferase complex

Identifiers
Symbol NuA4
Pfam PF09340
InterPro IPR015418

A complex having histone acetylase activity on chromatin, as well as ATPase, DNA helicase and structural DNA binding activities. The complex is thought to be involved in double-strand DNA break repair. Subunits of the human complex include HTATIP/TIP60, TRRAP, RUVBL1, BUVBL2, beta-actin and BAF53/ACTL6A. In yeast, the complex has 13 subunits, including the catalytic subunit Esa1 (homologous to human Tip60).[1]

Post-translational acetylation of histone H4 N-terminal tail in chromatin has been associated with several nuclear processes including transcription. We report the purification and characterization of a native multi- subunit complex (NuA4) from yeast that acetylates nucleosomal histone H4. NuA4 has an apparent molecu- lar mass of 1.3 MDa. All four conserved lysines of histone H4 can be acetylated by NuA4. We have identified the catalytic subunit of the complex as the product of ESA1 , an essential gene required for cell cycle progression in yeast. Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, we have identi- fied another subunit of the complex as the product of TRA1 , an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4–VP16-driven tran- scription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant. The function of the essential Esa1 protein as the HAT subunit of NuA4 and the presence of Tra1p, a putative [[transcrip- tion]] activator-interacting subunit, supports an essential link between nuclear H4 acetylation, transcriptional regulation and cell cycle control.[2]

References

  1. ↑ http://www.yeastgenome.org/go/GO:0035267/overview
  2. ↑ Allard, S; Utley, RT; Savard, J; Clarke, A; Grant, P; Brandl, CJ; Pillus, L; Workman, JL; Côté, J (1999). "NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p". EMBO J. 18: 5108–19. doi:10.1093/emboj/18.18.5108. PMC 1171581Freely accessible. PMID 10487762.
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