ChIP-seq of MYST acetyltransferases in RKO cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63722 | GEO | 2016/02/05
SECONDARY ACCESSION(S): PRJNA269250
REPOSITORIES: GEO
Similar Datasets
Project description:Genome-wide mapping of MYST acetyltransferase subunit BRPF3 in RKO synchronised cells. Genome-wide mapping of MYST acetyltransferase subunit BRPF3 in RKO synchronised cells.
2016-02-05 | E-GEOD-63722 | biostudies-arrayexpress
Project description:Histone acetyltransferases (HAT) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF-family of scaffold proteins. Their PHD-ZnKnuckle-PHD domain is essential for binding chromatin and restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region at the N-terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity from H4 to H3 tails, highlighting a crucial new role of associated subunits within HAT complexes, previously thought to be intrinsic to the catalytic subunit. Genome-wide mapping of MYST acetyltransferases subunits and H3K4me3 histone mark in RKO cells.
2013-10-09 | E-GEOD-47190 | biostudies-arrayexpress
Project description:Mutations in SET binding protein 1 (SETBP1) are associated with an adverse prognosis in myeloid malignancies. These mutations stabilize SETBP1 protein, driving increased expression of a progenitor-associated gene expression program through incompletely described mechanisms. A proteomic screen revealed interactions between SETBP1 and members of the MYST acetyltransferase complexes, including the catalytic subunits—KAT6A and KAT7. Mutant SETBP1 increases the localization of MYST complexes at known SETBP1 target genes, including the Hoxa cluster, where they drive increased histone acetylation and gene expression. Treatment of SETBP1D868N-expressing myeloid progenitors with MYST inhibitors reduced target gene expression. To establish the efficacy of MYST inhibition in vivo, we treated mice harboring a syngeneic SETBP1-mutant leukemia with the clinical-grade MYST inhibitor—PF-9363. This resulted in complete hematologic control and increased survival. MYST inhibition was also highly effective against a SETBP1-mutant PDX model. These studies identify MYST acetyltransferases as promising therapeutic targets in SETBP1-mutant malignancies.
2026-04-01 | GSE303627 | GEO
Project description:Mutations in SET binding protein 1 (SETBP1) are associated with an adverse prognosis in myeloid malignancies. These mutations stabilize SETBP1 protein, driving increased expression of a progenitor-associated gene expression program through incompletely described mechanisms. A proteomic screen revealed interactions between SETBP1 and members of the MYST acetyltransferase complexes, including the catalytic subunits—KAT6A and KAT7. Mutant SETBP1 increases the localization of MYST complexes at known SETBP1 target genes, including the Hoxa cluster, where they drive increased histone acetylation and gene expression. Treatment of SETBP1D868N-expressing myeloid progenitors with MYST inhibitors reduced target gene expression. To establish the efficacy of MYST inhibition in vivo, we treated mice harboring a syngeneic SETBP1-mutant leukemia with the clinical-grade MYST inhibitor—PF-9363. This resulted in complete hematologic control and increased survival. MYST inhibition was also highly effective against a SETBP1-mutant PDX model. These studies identify MYST acetyltransferases as promising therapeutic targets in SETBP1-mutant malignancies.
2026-04-01 | GSE303625 | GEO
Project description:Histone acetyltransferases (HAT) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF-family of scaffold proteins. Their PHD-ZnKnuckle-PHD domain is essential for binding chromatin and restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region at the N-terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity from H4 to H3 tails, highlighting a crucial new role of associated subunits within HAT complexes, previously thought to be intrinsic to the catalytic subunit.
2013-10-09 | GSE47190 | GEO
Project description:MYST lysine acetyltransferases (KATs) is a class of epigenetic enzymes critical for cellular function that constitute an emerging therapeutic target in cancer. Recently, several drug-like MYST inhibitors have been reported that show promise in a variety of preclinical models as well as in clinical trials of breast cancer. However, the comparative properties of these small molecules remain to be directly assessed. Here we apply an integrated profiling strategy to systematically define the potency and selectivity of drug-like MYST KAT inhibitors. First, we use optimized chemoproteomic profiling and histone acetylation biormarkers to study the industry-developed KAT inhibitor PF-9363. This revealed dose-dependent engagement of native KAT complexes, with hierarchical inhibition following the order KAT6A/B > KAT7 >> KAT8 > KAT5. Next, we demonstrate how PF-9363s ability to disrupt capture of MYST complex members in chemoproteomic experiments can be leveraged identify new candidate members of these complexes, including the transcription factor FOXK2. Applying insights from these studies to WM-8014, WM-1119 and WM-3835, which have been extensively applied in the literature as MYST probes, highlights unexpected cross-inhibition and suggests a new framework for how these small molecules and biomarkers may be applied to differentiate KAT6A/B and KAT7-dependent phenotypes. Finally, we benchmark the activity of PF-9363 in the NCI-60 cell line screen, providing evidence that its ability to inhibit the growth of cell lines that are resistant to other KAT inhibitors may derive from engagement of the essential KAT8 enzyme at high concentrations. Collectively, our studies indicate the potential for MYST KAT inhibitors to exhibit dose-dependent target engagement reminiscent of kinase inhibitors and specify assays and biomarkers for facile monitoring of selective and hierarchical effects.
2026-06-01 | PXD074488 | Pride
Project description:MYST lysine acetyltransferases (KATs) is a class of epigenetic enzymes critical for cellular function that constitute an emerging therapeutic target in cancer. Recently, several drug-like MYST inhibitors have been reported that show promise in a variety of preclinical models as well as in clinical trials of breast cancer. However, the comparative properties of these small molecules remain to be directly assessed. Here we apply an integrated profiling strategy to systematically define the potency and selectivity of drug-like MYST KAT inhibitors. First, we use optimized chemoproteomic profiling and histone acetylation biormarkers to study the industry-developed KAT inhibitor PF-9363. This revealed dose-dependent engagement of native KAT complexes, with hierarchical inhibition following the order KAT6A/B > KAT7 >> KAT8 > KAT5. Next, we demonstrate how PF-9363s ability to disrupt capture of MYST complex members in chemoproteomic experiments can be leveraged identify new candidate members of these complexes, including the transcription factor FOXK2. Applying insights from these studies to WM-8014, WM-1119 and WM-3835, which have been extensively applied in the literature as MYST probes, highlights unexpected cross-inhibition and suggests a new framework for how these small molecules and biomarkers may be applied to differentiate KAT6A/B and KAT7-dependent phenotypes. Finally, we benchmark the activity of PF-9363 in the NCI-60 cell line screen, providing evidence that its ability to inhibit the growth of cell lines that are resistant to other KAT inhibitors may derive from engagement of the essential KAT8 enzyme at high concentrations. Collectively, our studies indicate the potential for MYST KAT inhibitors to exhibit dose-dependent target engagement reminiscent of kinase inhibitors and specify assays and biomarkers for facile monitoring of selective and hierarchical effects.
2025-04-23 | MSV000097704 | MassIVE
Project description: Not available
| S-EPMC12478385 | biostudies-literature
Project description:We used ChIP-seq technology in order to map chromatin binding sites of the HBO1 MYST complex in the RKO cell line. We obtained a significant enrichment of the HBO1 signal right after TSS regions of genes and also In the proximal promoter region, with no signal on TSS. This enrichment also correlates with gene expression level. HBO1 signal in RKO cell line.
2012-03-15 | E-GEOD-33007 | biostudies-arrayexpress
Project description:To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance.
2025-07-03 | GSE246115 | GEO