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Molecular and Cellular Biology, December 2008, p. 7337-7344, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.00976-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Molecular Regulation of H3K4 Trimethylation by Wdr82, a Component of Human Set1/COMPASS{triangledown}

Min Wu,{dagger} Peng Fei Wang,{dagger} Jung Shin Lee, Skylar Martin-Brown, Laurence Florens, Michael Washburn, and Ali Shilatifard*

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110

Received 20 June 2008/ Returned for modification 27 July 2008/ Accepted 25 September 2008

In yeast, the macromolecular complex Set1/COMPASS is capable of methylating H3K4, a posttranslational modification associated with actively transcribed genes. There is only one Set1 in yeast; yet in mammalian cells there are multiple H3K4 methylases, including Set1A/B, forming human COMPASS complexes, and MLL1-4, forming human COMPASS-like complexes. We have shown that Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes. RNA interference-mediated knockdown of Wdr82 results in a reduction in the H3K4 trimethylation levels, although these cells still possess active MLL complexes. Comprehensive in vitro enzymatic studies with Set1 and MLL complexes demonstrated that the Set1 complex is a more robust H3K4 trimethylase in vitro than the MLL complexes. Given our in vivo and in vitro observations, it appears that the human Set1 complex plays a more widespread role in H3K4 trimethylation than do the MLL complexes in mammalian cells.


* Corresponding author. Mailing address: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110. Phone: (816) 926-4465. Fax: (816) 926-2080. E-mail: ash{at}stowers-institute.org

{triangledown} Published ahead of print on 6 October 2008.

{dagger} M.W. and P.F.W. contributed equally to this study.


Molecular and Cellular Biology, December 2008, p. 7337-7344, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.00976-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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