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Mol Cell Biol. 2013 May;33(10):2067-77. doi: 10.1128/MCB.01742-12. Epub 2013 Mar 18.

Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes.

Author information

1
Molecular Cancer Research, Netherlands Proteomics Center, Utrecht, The Netherlands.

Abstract

Methylation of lysine 4 on histone H3 (H3K4) at promoters is tightly linked to transcriptional regulation in human cells. At least six different COMPASS-like multisubunit (SET1/MLL) complexes that contain methyltransferase activity for H3K4 have been described, but a comprehensive and quantitative analysis of these SET1/MLL complexes is lacking. We applied label-free quantitative mass spectrometry to determine the subunit composition and stoichiometry of the human SET1/MLL complexes. We identified both known and novel, unique and shared interactors and determined their distribution and stoichiometry over the different SET1/MLL complexes. In addition to being a core COMPASS subunit, the Dpy30 protein is a genuine subunit of the NURF chromatin remodeling complex. Furthermore, we identified the Bod1 protein as a discriminator between the SET1B and SET1A complexes, and we show that the H3K36me-interactor Psip1 preferentially binds to the MLL2 complex. Finally, absolute protein quantification in crude lysates mirrors many of the observed SET1/MLL complex stoichiometries. Our findings provide a molecular framework for understanding the diversity and abundance of the different SET1/MLL complexes, which together establish the H3K4 methylation landscape in human cells.

PMID:
23508102
PMCID:
PMC3647974
DOI:
10.1128/MCB.01742-12
[Indexed for MEDLINE]
Free PMC Article

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