Reference: Takahashi YH, et al. (2009) Regulation of H3K4 trimethylation via Cps40 (Spp1) of COMPASS is monoubiquitination independent: implication for a Phe/Tyr switch by the catalytic domain of Set1. Mol Cell Biol 29(13):3478-86

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Abstract


The multiprotein complex Set1/COMPASS is the founding member of the histone H3 lysine 4 (H3K4) methyltransferases, whose human homologs include the MLL and hSet1 complexes. COMPASS can mono-, di-, and trimethylate H3K4, but transitioning to di- and trimethylation requires prior H2B monoubiquitination followed by recruitment of the Cps35 (Swd2) subunit of COMPASS. Another subunit, Cps40 (Spp1), interacts directly with Set1 and is only required for transitioning to trimethylation. To investigate how the Set1 and COMPASS subunits establish the methylation states of H3K4, we generated a homology model of the catalytic domain of Saccharomyces cerevisiae yeast Set1 and identified several key residues within the Set1 catalytic pocket that are capable of regulating COMPASS's activity. We show that Tyr1052, a putative Phe/Tyr switch of Set1, plays an essential role in the regulation of H3K4 trimethylation by COMPASS and that the mutation to phenylalanine (Y1052F) suppresses the loss of Cps40 in H3K4 trimethylation levels, suggesting that Tyr1052 functions together with Cps40. However, the loss of H2B monoubiquitination is not suppressed by this mutation, while Cps40 is stably assembled in COMPASS on chromatin, demonstrating that Tyr1052- and Cps40-mediated H3K4 trimethylation takes place following and independently of H2B monoubiquitination. Our studies provide a molecular basis for the way in which H3K4 trimethylation is regulated by Tyr1052 and the Cps40 subunit of COMPASS.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Takahashi YH, Lee JS, Swanson SK, Saraf A, Florens L, Washburn MP, Trievel RC, Shilatifard A
Primary Lit For
SWD2 | SET1 | SPP1 | BRE2 | COMPASS complex

Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 9 entries for 10 genes

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InteractorInteractorAssayAnnotationActionModification

MudPIT

BRE2SPP1Affinity Capture-MSmanually curatedBait-HitNo Modification
HHT1SET1Biochemical Activitymanually curatedHit-Baitmethylated residue

MudPIT

SDC1BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification

MudPIT

SET1BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification
SET1HHT2Biochemical Activitymanually curatedBait-Hitmethylated residue

MudPIT

SHG1BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification

MudPIT

SWD1BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification

MudPIT

SWD2BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification

MudPIT

SWD3BRE2Affinity Capture-MSmanually curatedHit-BaitNo Modification
Showing 1 to 9 of 9 entries