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| Subject Categories: Chromatin & Transcription |
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| The EMBO Journal
(2005) 24, 1222–1231, doi:10.1038/sj.emboj.7600607 Published online 3 March 2005 |
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| Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains |
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| Alisha Schlichter1, 2 and Bradley R Cairns1, 2 |
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1 Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA 2 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA To whom correspondence should be addressed Bradley R Cairns, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Room 4362, HCI, 2000 Circle of Hope, Salt Lake City, UT 84112-0555, USA. Tel.: +1 801 585 1822; Fax: +1 801 585 6410; E-mail: brad.cairns@hci.utah.edu Received 15 December 2004; Accepted 9 February 2005; Published online 3 March 2005. |
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| Abstract |
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| Trimethylation of lysine 4 of histone H3 occurs at the 5' 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 SET1D 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 SET1D 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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| Keywords: chromatin, methylation, RRM, RSC, Set1 |
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