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wdr5 in 6  (TargetMol)


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    TargetMol wdr5 in 6
    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or <t>WDR5-mediated</t> H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and <t>WDR5-IN-6).</t> d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).
    Wdr5 In 6, supplied by TargetMol, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/wdr5 in 6/product/TargetMol
    Average 94 stars, based on 1 article reviews
    wdr5 in 6 - by Bioz Stars, 2026-03
    94/100 stars

    Images

    1) Product Images from "SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma"

    Article Title: SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma

    Journal: bioRxiv

    doi: 10.64898/2026.01.22.701194

    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).
    Figure Legend Snippet: a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).

    Techniques Used: Transduction, Knockdown, Control, shRNA, Expressing, Plasmid Preparation, Activity Assay, Inhibition, Ubiquitin Proteomics, Methylation, Mutagenesis, Transformation Assay, Western Blot, Quantitative Proteomics



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    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or <t>WDR5-mediated</t> H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and <t>WDR5-IN-6).</t> d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).
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    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or <t>WDR5-mediated</t> H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and <t>WDR5-IN-6).</t> d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).
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    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or <t>WDR5-mediated</t> H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and <t>WDR5-IN-6).</t> d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).
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    Image Search Results


    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).

    Journal: bioRxiv

    Article Title: SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma

    doi: 10.64898/2026.01.22.701194

    Figure Lengend Snippet: a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).

    Article Snippet: The following compounds were used in this study: SGF29-IN-1 (cat# HY-158009, MedChemExpress), GSK4027 (cat# SML2018, Sigma Aldrich), CPTH2 (cat# J65939LB0, ThermoFisher), garcinol (cat# 14076, Active Motif), USP22si-02 (cat# SML3875, Sigma Aldrich), WDR5-IN-4 (WIN site inhibitor, cat# HY-111753, MedChemExpress), WDR5-IN-6 (WBM site inhibitor, cat# T77495, TargetMol), OICR9429 (cat# T6916, TargetMol), WM586 (WDR5/Myc inhibitor, cat# HY-153728, MedChemExpress), YM-53601 (cat# HY-100313A, MedChemExpress), NB-598 (cat# HY-16343, MedChemExpress), terbinafine (cat# T3677, TCI Chemicals), Atorvastatin (cat# SML3030, Sigma Aldrich), and Pitavastatin (cat# AMBH2D6EF677, Ambeed)

    Techniques: Transduction, Knockdown, Control, shRNA, Expressing, Plasmid Preparation, Activity Assay, Inhibition, Ubiquitin Proteomics, Methylation, Mutagenesis, Transformation Assay, Western Blot, Quantitative Proteomics

    a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).

    Journal: bioRxiv

    Article Title: SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma

    doi: 10.64898/2026.01.22.701194

    Figure Lengend Snippet: a, Growth curves of SU-DIPGXIII cells transduced with shRNAs to knockdown both KAT2A and KAT2B, showing significantly reduced growth compared to control shRNA-transduced cells. b, Number of live SU-DIPGXIII+Cas9 cells expressing a control plasmid (HA/flag-GFP) or sgRNAs to KO SAGA-associated acetyltransferase activity ( TADA2B sgRNAs), or de-ubiquitinase activity ( ENY2 sgRNA). c, Schematic illustrating inhibition of histone-modifying modules of SAGA/ATAC complexes using chemical probes to target SAGA/ATAC-dependent histone acetylation (GSK4027, CPTH2, garcinol), SAGA-dependent H2A/H2B de-ubiquitination (USP22si-02), or WDR5-mediated H3K4me3 methylation (OICR-9529, WM856, WDR5-IN-4, and WDR5-IN-6). d, Average normalized cell viability from CellTiter-Glo assays conducted seven days after starting treatment of H3K27M mutant cells (teal curves) or non-transformed, H3 wildtype, control cells (black curves) with increasing doses of the KAT2A/2B bromodomain-targeting acetyltransferase inhibitor, GSK4027. e, Immunoblots confirming that treatment of BT245 cells with GSK4027 reduced H3K9ac in a dose-dependent manner, but not total H3 or SGF29 protein abundance. f-h, Dose response curves showing inhibition of H3K27M mutant DMG cell viability, but no effect on control H3 wild-type cells (black curves) following seven days of treatment with the DUB inhibitor, USP22i-S02 ( f, yellow curves), the WDR5 WIN site inhibitor, WDR5-IN-4 ( g, blue curves), or the WDR5 WBM site inhibitor, WDR5-IN-6 ( h, blue curves). i-j Average number of live SU-DIPGXIIIP*+ZsG/luc cells ( i ), and average BT245 ( j ) cell viability (CellTiter-Glo) following treatment with combinations of GSK4027 and USP22si-02 to simultaneously target both SAGA/ATAC-dependent histone acetyltransferase activity and SAGA-dependent H2A/H2B de-ubiquitination. k-l, BLISS synergy plots showing a combined effect of GSK4027 and WDR5-IN-6 treatment in reducing SU-DIPGXIIIP*+ZsG/luc growth ( k, **p<1.74×10 -3 ), and a combined effect of GSK4027 and WDR5-IN-4 treatment in reducing BT245 cell growth ( l , ****p<2.5×10 -10 ).

    Article Snippet: The following compounds were used in this study: SGF29-IN-1 (cat# HY-158009, MedChemExpress), GSK4027 (cat# SML2018, Sigma Aldrich), CPTH2 (cat# J65939LB0, ThermoFisher), garcinol (cat# 14076, Active Motif), USP22si-02 (cat# SML3875, Sigma Aldrich), WDR5-IN-4 (WIN site inhibitor, cat# HY-111753, MedChemExpress), WDR5-IN-6 (WBM site inhibitor, cat# T77495, TargetMol), OICR9429 (cat# T6916, TargetMol), WM586 (WDR5/Myc inhibitor, cat# HY-153728, MedChemExpress), YM-53601 (cat# HY-100313A, MedChemExpress), NB-598 (cat# HY-16343, MedChemExpress), terbinafine (cat# T3677, TCI Chemicals), Atorvastatin (cat# SML3030, Sigma Aldrich), and Pitavastatin (cat# AMBH2D6EF677, Ambeed)

    Techniques: Transduction, Knockdown, Control, shRNA, Expressing, Plasmid Preparation, Activity Assay, Inhibition, Ubiquitin Proteomics, Methylation, Mutagenesis, Transformation Assay, Western Blot, Quantitative Proteomics