Genome-wide map of HBO1 in cancer derived human cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33007 | GEO | 2012/03/15
SECONDARY ACCESSION(S): PRJNA155519
REPOSITORIES: GEO
Similar Datasets
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:Chronic myelomonocytic leukemia (CMML) is an incurable hematopoietic stem cell malignancy. We identified a novel NUP98-HBO1 fusion from a patient with CMML. HBO1, a histone acetyltransferase (HAT) which belongs to the MYST family, is the first NUP98 fusion partner encodes HAT. To determine the effect of the NUP98-HBO1 fusion on downstream target gene regulation, we performed gene expression array analysis of NUP98-HBO1-transduced human cord blood (CB) CD34+ cells.
2019-03-13 | GSE112909 | 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. Genome-wide mapping of MYST acetyltransferases subunits and H3K4me3 histone mark in RKO cells.
2013-10-09 | E-GEOD-47190 | biostudies-arrayexpress
Project description:Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by transcriptional dysregulation resulting in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, with most showing modest efficacy due to an inability to effectively eradicate leukaemia stem cells (LSC). To specifically identify novel dependencies in LSC we screened a bespoke library of small hairpin RNAs (shRNAs) targeting chromatin regulators in a unique ex vivo model of LSC. We identified the MYST acetyltransferases HBO1 (KAT7) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance ex vivo and conditional ablation of HBO1 confirmed its requirement for LSC maintenance in vivo. CRISPR domain screening identified the histone acetyltransferases (HAT) domain of HBO1 as being essential to acetylate histone H3K14, which is required for the expression of the key genes including HOXA9 and HOXA10 that maintain the immature phenotype and self-renewal properties of LSC. To leverage this dependency therapeutically we developed highly potent small molecule inhibitors of HBO1 and provide structural data to demonstrate their mode of activity as competitive analogues of acetyl-CoA. These inhibitors phenocopy our genetic data and show efficacy in a broad range of human cell lines and primary patient samples encompassing the most common genetic subtypes of AML.
2019-12-18 | GSE120812 | GEO
Project description:Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by transcriptional dysregulation resulting in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, with most showing modest efficacy due to an inability to effectively eradicate leukaemia stem cells (LSC). To specifically identify novel dependencies in LSC we screened a bespoke library of small hairpin RNAs (shRNAs) targeting chromatin regulators in a unique ex vivo model of LSC. We identified the MYST acetyltransferases HBO1 (KAT7) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance ex vivo and conditional ablation of HBO1 confirmed its requirement for LSC maintenance in vivo. CRISPR domain screening identified the histone acetyltransferases (HAT) domain of HBO1 as being essential to acetylate histone H3K14, which is required for the expression of the key genes including HOXA9 and HOXA10 that maintain the immature phenotype and self-renewal properties of LSC. To leverage this dependency therapeutically we developed highly potent small molecule inhibitors of HBO1 and provide structural data to demonstrate their mode of activity as competitive analogues of acetyl-CoA. These inhibitors phenocopy our genetic data and show efficacy in a broad range of human cell lines and primary patient samples encompassing the most common genetic subtypes of AML.
2019-12-18 | GSE120811 | GEO
Project description:Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by transcriptional dysregulation resulting in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, with most showing modest efficacy due to an inability to effectively eradicate leukaemia stem cells (LSC). To specifically identify novel dependencies in LSC we screened a bespoke library of small hairpin RNAs (shRNAs) targeting chromatin regulators in a unique ex vivo model of LSC. We identified the MYST acetyltransferases HBO1 (KAT7) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance ex vivo and conditional ablation of HBO1 confirmed its requirement for LSC maintenance in vivo. CRISPR domain screening identified the histone acetyltransferases (HAT) domain of HBO1 as being essential to acetylate histone H3K14, which is required for the expression of the key genes including HOXA9 and HOXA10 that maintain the immature phenotype and self-renewal properties of LSC. To leverage this dependency therapeutically we developed highly potent small molecule inhibitors of HBO1 and provide structural data to demonstrate their mode of activity as competitive analogues of acetyl-CoA. These inhibitors phenocopy our genetic data and show efficacy in a broad range of human cell lines and primary patient samples encompassing the most common genetic subtypes of AML.
2019-12-18 | GSE139118 | GEO
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:Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a “writer” of Kbz in mammalian cells. In addition, we report the first benzoylome in mammalian cells, identifying 1747 Kbz sites, among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify key regulatory elements of the Kbz pathway, and reveal new enzymatic activity and functions of HBO1 in cellular physiology.
2022-10-14 | PXD034187 | Pride
Project description:We find that 499 genes are up-regulated and 457 are down-regulated in response to over-expression of JADE1, while 397 genes are up-regulated and 385 are down-regulated after HBO1 knock-down. For each condition - HBO1 siRNA treatment or JADE1 over-expression - two biological replicates were analyzed in duplicate.
2012-03-15 | E-GEOD-33220 | biostudies-arrayexpress
Project description:Genome-wide mapping of MYST acetyltransferase subunit BRPF3 in RKO synchronised cells.
2016-02-05 | GSE63722 | GEO