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HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia

ABSTRACT: HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia

PROVIDER: PRJNA915390 | ENA |

REPOSITORIES: ENA

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HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [RNA-seq]

Project description:This study identifies HOXA9 protein interactome in acute myeloid leukemia cells. Integrated genomic, transcriptomic and proteomic analyses further demonstrated that the HOXA9-SAFB-chromatin complex associates with NuRD and HP1γ to repress the expression of factors associated with differentiation and apoptosis in leukemia maintenance.

2022-12-27 | GSE221700 | GEO

HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [CUT&RUN/ChIP-Seq]

2022-12-27 | GSE221697 | GEO

HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [RNA-seq]

Project description:HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [RNA-seq]

| PRJNA915392 | ENA

HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia.

Project description:HOXA9 is commonly upregulated in acute myeloid leukemia (AML), in which it confers a poor prognosis. Characterizing the protein interactome of endogenous HOXA9 in human AML, we identified a chromatin complex of HOXA9 with the nuclear matrix attachment protein SAFB. SAFB perturbation phenocopied HOXA9 knockout to decrease AML proliferation, increase differentiation and apoptosis in vitro, and prolong survival in vivo. Integrated genomic, transcriptomic, and proteomic analyses further demonstrated that the HOXA9-SAFB (H9SB)-chromatin complex associates with nucleosome remodeling and histone deacetylase (NuRD) and HP1γ to repress the expression of factors associated with differentiation and apoptosis, including NOTCH1, CEBPδ, S100A8, and CDKN1A. Chemical or genetic perturbation of NuRD and HP1γ-associated catalytic activity also triggered differentiation, apoptosis, and the induction of these tumor-suppressive genes. Importantly, this mechanism is operative in other HOXA9-dependent AML genotypes. This mechanistic insight demonstrates the active HOXA9-dependent differentiation block as a potent mechanism of disease maintenance in AML that may be amenable to therapeutic intervention by targeting the H9SB interface and/or NuRD and HP1γ activity.

| S-EPMC10113176 | biostudies-literature

HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [CUT&RUN/ChIP-Seq]

Project description:HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia [CUT&RUN/ChIP-Seq]

| PRJNA915391 | ENA

HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-27 | GSE221701 | GEO

The nuclear matrix protein SAFB maintains heterochromatin architecture through RNA-dependent phase separation [HiChIP]

Project description:Eukaryotic chromosomes fold into topologically associating domains (TADs), which further gather in active (A) or inactive (B) genomic compartments. Here we show that Scaffold Attachment Factor B (SAFB), a nuclear matrix-associated protein with RNA binding functions, modulates global chromatin condensation in a dosage-dependent manner. Upon the depletion of SAFB, the genome coverage of Lamina-associated-domains (LADs) decreases from 53.33% to 45.93%, and both inter- and intra-TAD chromatin-chromatin interactions in compartment B decrease significantly. In the nucleus, SAFB favorably co-localizes with H3K9me3, a marker of heterochromatin, and the disruption of SAFB leads to a collapse of H3K9me3 foci. Furthermore, we show that SAFB proteins can form liquid-liquid phase separation in the cell and in vitro. Intriguingly, SAFB interacts with RNAs from repetitive elements enriched in heterochromatin (e.g., Major Satellites and LINE1), which can promote SAFB-mediated phase separation, depending on the density of SAFB recognizing motifs in the RNAs.

2019-12-01 | GSE141113 | GEO

The nuclear matrix protein SAFB maintains heterochromatin architecture through RNA-dependent phase separation [RIP-seq]

2019-12-01 | GSE141084 | GEO

The nuclear matrix protein SAFB maintains heterochromatin architecture through RNA-dependent phase separation [Hi-C]

2019-12-01 | GSE141080 | GEO

The nuclear matrix protein SAFB maintains heterochromatin architecture through RNA-dependent phase separation [H3K9me3 ChIP-seq]

2019-12-01 | GSE141104 | GEO