Boyes J, Byfield P, Nakatani Y, Ogryzko V
Section of Gene Function and Regulation, Chester Beatty Laboratories at The Institute of Cancer Research, London, UK.
Nature. 1998 Dec 10;396(6711):594-8. doi: 10.1038/25166.
Modification of histones, DNA-binding proteins found in chromatin, by addition of acetyl groups occurs to a greater degree when the histones are associated with transcriptionally active DNA. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p, PCAF, TAF(II)250 and p300/CBP. These acetyltransferases also modify certain transcription factors (TFIIEbeta, TFIIF, EKLF and p53). GATA-1 is an important transcription factor in the haematopoietic lineage and is essential for terminal differentiation of erythrocytes and megakaryocytes. It is associated in vivo with the acetyltransferase p300/CBP. Here we report that GATA-1 is acetylated in vitro by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1-DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated in vivo and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and in vivo function of GATA-1. We propose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes.
组蛋白是染色质中发现的DNA结合蛋白，当组蛋白与转录活性DNA相关联时，通过添加乙酰基对其进行修饰的程度会更高。在理解这种乙酰化如何介导方面的一个突破是发现各种转录共激活蛋白具有内在的组蛋白乙酰转移酶活性（例如，Gcn5p、PCAF、TAF(II)250和p300/CBP）。这些乙酰转移酶还会修饰某些转录因子（TFIIEbeta、TFIIF、EKLF和p53）。GATA-1是造血谱系中的一种重要转录因子，对红细胞和巨核细胞的终末分化至关重要。它在体内与乙酰转移酶p300/CBP相关联。在此我们报告GATA-1在体外被p300乙酰化。这显著增加了与DNA结合的GATA-1的量，并改变了GATA-1-DNA复合物的迁移率，提示GATA-1发生了构象变化。GATA-1在体内也被乙酰化，并且乙酰化直接刺激GATA-1依赖的转录。对重要乙酰化残基的诱变表明GATA-1的乙酰化与其体内功能之间存在关联。我们提出转录因子的乙酰化可以改变这些因子与DNA之间以及不同转录因子之间的相互作用，并且是转录和分化过程的一个组成部分。
