共 30 条
Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains
被引:80
作者:

Schlichter, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA

Cairns, BR
论文数: 0 引用数: 0
h-index: 0
机构: Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
机构:
[1] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
[2] Univ Utah, Sch Med, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA
关键词:
chromatin;
methylation;
RRM;
RSC;
Set1;
D O I:
10.1038/sj.emboj.7600607
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:
Trimethylation of lysine 4 of histone H3 occurs at the 50 end of active genes and is catalyzed by Set1 in Saccharomyces cerevisiae. Trimethylation requires histone H2B ubiquitylation and the PAF1 complex, which are linked to transcription elongation, but how they activate Set1 is not known. Set1 also bears several conserved domains with uncharacterized contributions to activity. Here, we isolated dominant hyperactive SET1(D) alleles, which revealed a complex interplay among Set1 regulatory domains. Remarkably, the RNA-recognition motif (RRM) of Set1 is required for H3K4 trimethylation, but not dimethylation. Also, a central autoinhibitory domain was identified that opposes RRM function by inhibiting trimethylation. Furthermore, a G990E replacement in the catalytic domain conferred Set1 hyperactivity and restored trimethylation to a Set1 derivative bearing mutations in the RRM domain. Surprisingly, certain SET1(D) alleles also partially restored trimethylation to strains lacking histone H2B ubiquitylation or Paf1. Taken together, our data suggest that the catalytic domain of Set1 integrates opposing inputs from the RRM and autoinhibitory domains to link properly H3K4 methylation to the transcript elongation process.
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页码:1222 / 1231
页数:10
相关论文
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