A comprehensive library of histone mutants identifies nucleosomal residues required for H3K4 methylation

被引:153
作者
Nakanishi, Shima [1 ]
Sanderson, Brian W. [1 ]
Delventhal, Kym M. [1 ]
Bradford, William D. [1 ]
Staehling-Hampton, Karen [1 ]
Shilatifard, Ali [1 ]
机构
[1] Stowers Inst Med Res, Kansas City, MO 64110 USA
关键词
D O I
10.1038/nsmb.1454
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Methylation of histone 3 lysine 4 (H3K4) by yeast Set1-COMPASS requires prior monoubiquitination of histone H2B. To define whether other residues within the histones are also required for H3K4 methylation, we systematically generated a complete library of the alanine substitutions of all of the residues of the four core histones in Saccharomyces cerevisiae. From this study we discovered that 18 residues within the four histones are essential for viability on complete growth media. We also identified several cis-regulatory residues on the histone H3 N-terminal tail, including histone H3 lysine 14 (H3K14), which are required for normal levels of H3K4 trimethylation. Several previously uncharacterized trans-regulatory residues on histones H2A and H2B form a patch on nucleosomes and are required for normal levels of methylation mediated by COMPASS. This library will be a valuable tool for defining the role of histone residues in processes requiring chromatin.
引用
收藏
页码:881 / 888
页数:8
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