Duina Andrea A, Winston Fred
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Mol Cell Biol. 2004 Jan;24(2):561-72. doi: 10.1128/MCB.24.2.561-572.2004.
We have isolated new histone H3 mutants in Saccharomyces cerevisiae that confer phenotypes indicative of transcriptional defects. Here we describe the characterization of one such mutant, encoded by the hht2-11 allele, which contains the single amino acid change L61W in the globular domain of H3. Whole-genome expression analyses show that the hht2-11 mutation confers pleiotropic transcriptional defects and that many of the genes it affects are normally controlled by the Swi/Snf chromatin remodeling complex. Furthermore, we show that Swi/Snf occupancy at two promoters, PHO84 and SER3, is reduced in hht2-11 mutants. Detailed studies of the PHO84 promoter suggest that the hht2-11 mutation impairs Swi/Snf association with chromatin in a direct fashion. Taken together, our results strongly suggest that the integrity of the globular domain of histone H3 is an important determinant in the ability of Swi/Snf to associate with chromatin.
我们在酿酒酵母中分离出了新的组蛋白H3突变体，这些突变体表现出转录缺陷的表型。在此，我们描述了其中一个由hht2-11等位基因编码的突变体的特征，该突变体在H3的球状结构域中包含单个氨基酸变化L61W。全基因组表达分析表明，hht2-11突变导致多效性转录缺陷，且它所影响的许多基因通常由Swi/Snf染色质重塑复合体调控。此外，我们发现hht2-11突变体中Swi/Snf在两个启动子PHO84和SER3上的占据率降低。对PHO84启动子的详细研究表明，hht2-11突变以直接方式损害了Swi/Snf与染色质的结合。综上所述，我们的结果强烈表明组蛋白H3球状结构域的完整性是Swi/Snf与染色质结合能力的重要决定因素。
