1. Academic Validation
  2. Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS

Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS

  • Mol Cell Biol. 2008 Dec;28(24):7337-44. doi: 10.1128/MCB.00976-08.
Min Wu 1 Peng Fei Wang Jung Shin Lee Skylar Martin-Brown Laurence Florens Michael Washburn Ali Shilatifard
Affiliations

Affiliation

  • 1 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
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.

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