Unique Role of the WD-40 Repeat Protein 5 (WDR5) Subunit within the Mixed Lineage Leukemia 3 (MLL3) Histone Methyltransferase Complex.

The Journal of Biological Chemistry
Stephen A Shinsky, Michael S Cosgrove

Abstract

The MLL3 (mixed lineage leukemia 3) protein is a member of the human SET1 family of histone H3 lysine 4 methyltransferases and contains the conserved WDR5 interaction (Win) motif and the catalytic suppressor of variegation, enhancer of zeste, trithorax (SET) domain. The human SET1 family includes MLL1-4 and SETd1A/B, which all interact with a conserved subcomplex containing WDR5, RbBP5, Ash2L, and DPY-30 (WRAD) to form the minimal core complex required for full methyltransferase activity. However, recent evidence suggests that the WDR5 subunit may not be utilized in an identical manner within all SET1 family core complexes. Although the roles of WDR5 within the MLL1 core complex have been extensively studied, not much is known about the roles of WDR5 in other SET1 family core complexes. In this investigation, we set out to characterize the roles of the WDR5 subunit in the MLL3 core complex. We found that unlike MLL1, the MLL3 SET domain assembles with the RbBP5/Ash2L heterodimer independently of the Win motif-WDR5 interaction. Furthermore, we observed that WDR5 inhibits the monomethylation activity of the MLL3 core complex, which is dependent on the Win motif. We also found evidence suggesting that the WRAD subcomplex catalyzes...Continue Reading

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Citations

Feb 6, 2017·Protein Science : a Publication of the Protein Society·Masoud VedadiTaraneh Hajian
Jun 30, 2018·The Journal of Biological Chemistry·Homa RahnamounShannon M Lauberth
May 13, 2020·Journal of Cellular and Molecular Medicine·Han WangShuai Chen
Apr 18, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Hao Jiang

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Methods Mentioned

BETA
x-ray scattering
amidation
size exclusion chromatography

Software Mentioned

Primus
DAMMIN
SEDFIT
ATSAS Package EMBL
Chimera
AUC
DAMAVER
mMass
GeneScript
ATSAS

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