Brownell J E, Zhou J, Ranalli T, Kobayashi R, Edmondson D G, Roth S Y, Allis C D
Department of Biology, University of Rochester, New York, 14627, USA.
Cell. 1996 Mar 22;84(6):843-51. doi: 10.1016/s0092-8674(00)81063-6.
We report the cloning of a transcription-associated histone acetyltransferase type A(HAT A). This Tetrahymena enzyme is strikingly homologous to the yeast protein Gcn5, a putative transcriptional adaptor, and we demonstrate that recombinant Gcn5p possesses HAT activity. Both the ciliate enzyme and Gcn5p contain potential active site residues found in other acetyltransferases and a highly conserved bromodomain. The presence of this domain in nuclear A-type HATs, but not in cytoplasmic B-type HATs, suggests a mechanism whereby HAT A is directed to chromatin to facilitate transcriptional activation. These findings shed light on the biochemical function of the evolutionarily conserved Gcn5p-Ada complex, directly linking histone acetylation to gene activation, and indicate that histone acetylation is a targeted phenomenon.
我们报道了一种转录相关的 A 型组蛋白乙酰转移酶（HAT A）的克隆。这种嗜热四膜虫酶与酵母蛋白 Gcn5 显著同源，Gcn5 是一种假定的转录衔接子，并且我们证明重组 Gcn5p 具有 HAT 活性。纤毛虫酶和 Gcn5p 都含有在其他乙酰转移酶中发现的潜在活性位点残基以及一个高度保守的溴结构域。核 A 型 HAT 中存在该结构域，而细胞质 B 型 HAT 中不存在，这提示了一种机制，通过该机制 HAT A 被导向染色质以促进转录激活。这些发现揭示了进化上保守的 Gcn5p - Ada 复合物的生化功能，直接将组蛋白乙酰化与基因激活联系起来，并表明组蛋白乙酰化是一种靶向现象。
