Molecular regulation of H3k4 trimethylation by Wdr82, a component of human set1/COMPASS

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7337-7344
Number of pages8
JournalMolecular and cellular biology
Volume28
Issue number24
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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