Winkler G Sebastiaan, Kristjuhan Arnold, Erdjument-Bromage Hediye, Tempst Paul, Svejstrup Jesper Q
Cancer Research UK., London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3517-22. doi: 10.1073/pnas.022042899.
The elongating, hyperphosphorylated form of RNA polymerase II is associated with the Elongator complex, which has the histone acetyltransferase (HAT) Elp3 as a subunit. Here we show that, in contrast to the isolated Elp3 subunit, the activity of intact Elongator complex is directed specifically toward the amino-terminal tails of histone H3 and H4, and that Elongator can acetylate both core histones and nucleosomal substrates. The predominant acetylation sites are lysine-14 of histone H3 and lysine-8 of histone H4. The three smallest Elongator subunits--Elp4, Elp5, and Elp6--are required for HAT activity, and Elongator binds to both naked and nucleosomal DNA. By using chromatin immunoprecipitation, we show that the levels of multiply acetylated histone H3 and H4 in chromatin are decreased in vivo in yeast cells lacking ELP3.
RNA聚合酶II的延伸型、高度磷酸化形式与延伸因子复合物相关,该复合物以组蛋白乙酰转移酶(HAT)Elp3作为一个亚基。我们在此表明,与分离的Elp3亚基不同,完整的延伸因子复合物的活性特异性地作用于组蛋白H3和H4的氨基末端尾巴,并且延伸因子能够使核心组蛋白和核小体底物乙酰化。主要的乙酰化位点是组蛋白H3的赖氨酸-14和组蛋白H4的赖氨酸-8。HAT活性需要延伸因子复合物的三个最小亚基——Elp4、Elp5和Elp6,并且延伸因子复合物能与裸露的和核小体的DNA结合。通过染色质免疫沉淀,我们表明在缺乏ELP3的酵母细胞中,染色质中多重乙酰化的组蛋白H3和H4的水平在体内会降低。