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AML1/ETO, AML1, and HEB binding patterns on chromosme 19

ABSTRACT: Approximately 20% of Acute Myelogenous Leukemia (AML) cases carry the t(8;21) translocation, which involves the AML1 and ETO genes, and express the resulting AML1/ETO fusion protein that functions as a transcriptional repressor by recruiting NCoR/SMRT/HDAC complexes to DNA. We used ChIP-chip to identify the determinants of AML1/ETO binding on a contiguous DNA region (chromosome 19). AML1/ETO binding regions are characterized by a specific sequence signature that includes the presence of the consensus binding sites for the AML1 and HEB transcription factors. We therefore assessed the binding patterns of AML1 and HEB on chromosome 19. A specific chromatin modification (tri-methylation of lysine 4 on histone 3 = 3MetK4) was also studied in U937 cells expressing AML1/ETO in order to correlate the identified binding profiles with active transcription sites. Keywords: ChIP-chip

ORGANISM(S): Homo sapiens

PROVIDER: GSE10578 | GEO | 2008/11/28

SECONDARY ACCESSION(S): PRJNA108837

REPOSITORIES: GEO

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AML1/ETO, AML1, and HEB binding patterns on chromosme 19

Project description:Approximately 20% of Acute Myelogenous Leukemia (AML) cases carry the t(8;21) translocation, which involves the AML1 and ETO genes, and express the resulting AML1/ETO fusion protein that functions as a transcriptional repressor by recruiting NCoR/SMRT/HDAC complexes to DNA. We used ChIP-chip to identify the determinants of AML1/ETO binding on a contiguous DNA region (chromosome 19). AML1/ETO binding regions are characterized by a specific sequence signature that includes the presence of the consensus binding sites for the AML1 and HEB transcription factors. We therefore assessed the binding patterns of AML1 and HEB on chromosome 19. A specific chromatin modification (tri-methylation of lysine 4 on histone 3 = 3MetK4) was also studied in U937 cells expressing AML1/ETO in order to correlate the identified binding profiles with active transcription sites. Keywords: ChIP-chip A U937 cell line that conditionally expresses HA-tagged AML1/ETO under the control of the mouse metallothionine promoter (U937-A1E) (Alcalay et al., J.Clin.Invest, 2003,112, 1751-1761) was used. Cell lines were treated for 8h with 100uM ZnSO4 to induce transgene expression in U937-A1E. We performed ChIP using anti-HA, anti-ETO, anti-AML1/RUNX1, anti-HEBor anti-3MetK4 antibodies. ChIP products were then PCR amplified, labeled with Cy3/Cy5 fluorescent dyes and hybridized to the NimbleGen custom made NGS_HG17_Chr.19Array. U937-Mt cells, which carry the empty vector, served as control (C) for non-specific antibody binding. Each sample identifier indicates Antibody_Cell line (example: HA_A1E = ChIP using anti HA antibody in U937-A1E cells; HA_C = ChIP using anti HA antibody in U937-Mt control cells)

2008-11-27 | E-GEOD-10578 | biostudies-arrayexpress

Analysis of expression levels of genes on chromosome 19 in U937 cells expressing AML1/ETO

2008-11-28 | GSE10579 | GEO

Gene expression profile and DNA binding pattern of AML1/ETO in U937 cells

Project description:This SuperSeries is composed of the following subset Series: GSE10520: Genes regulated by AML1/ETO in U937 cells GSE10537: Gene expression profiling of AML1/ETO regulated genes and binding pattern on human promoters in U937 cells GSE10578: AML1/ETO, AML1, and HEB binding patterns on chromosme 19 GSE10579: Analysis of expression levels of genes on chromosome 19 in U937 cells expressing AML1/ETO Keywords: SuperSeries Refer to individual Series

2010-06-24 | E-GEOD-10537 | biostudies-arrayexpress

Analysis of expression levels of genes on chromosome 19 in U937 cells expressing AML1/ETO

2010-06-24 | E-GEOD-10579 | biostudies-arrayexpress

A Stable Transcription Factor Complex Nucleated by Dimeric AML1-ETO Controls Leukaemogenesis

Project description:AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukemia, is a transcription factor implicated in both gene repression and activation. We now show that, in leukemic cells, AML1-ETO resides in and functions through a stable protein complex (AETFC) that contains several hematopoietic transcription factors and cofactors. In conjunction with biochemical and leukemia pathological studies, the ChIP-seq and RNA-seq analyses of the AETFC components in leukemic cells reveal that these components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, colocalize genome-wide, cooperatively regulate gene expression, and contribute to leukemogenesis. RNA-seq analyses gene expression upon knockdown of each AETFC component, including AML1-ETO, HEB, E2A, LYL1, LDB1 and LMO2, and double-knockdown of HEB and E2A, in Kasumi-1 cells. ChIP-seq analyses of four AETFC components, namely AML1-ETO, HEB, E2A and LMO2, in Kasumi-1 cells.

2013-06-20 | E-GEOD-43834 | biostudies-arrayexpress

Oncofusion protein AML1-ETO targets ERG factor binding sites in AML

Project description:ERG has been identified as an essential factor for the function and maintenance of adult hematopoietic stem cells and high ERG expression is a negative prognostic marker for treatment outcome in AML. The molecular function of ERG and its interplay with other factors is however largely unknown. Here we demonstrate that ERG has cell type specific distributions in normal CD34+ myeloid progenitors and in AML cells and identify ERG as a potential pioneering protein for binding of oncofusion protein complexes. In addition, we identify H3 acetylation as the epigenetic mark preferentially associated with ERG binding. This intimate connection between ERG binding and H3 acetylation implies that one of the molecular strategies of the oncofusion proteins PML-RARa and AML1-ETO could involve the targeting of histone deacetylase activities to ETS factor bound hematopoietic regulatory sites. Examination of AML1-ETO, RUNX1, CBFb, HEB, FLI1 and ERG binding sites (ChIP-seq) in leukemic and normal hematopoietic cells, association with chromatin modifications and expression (RNA-seq) analysis of an AML1-ETO expressing cell line (SKNO-1)

2012-09-18 | E-GEOD-23730 | biostudies-arrayexpress

Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia

Project description:The AML1/ETO fusion protein is essential to the development of acute myeloid leukemia (AML), and is well recognized for its dominant-negative effect on the co-existing wild-type protein AML1. However, the involvement of wild-type AML1 in AML1/ETO-driven leukemogenesis remains elusive. Through chromatin immunoprecipitation sequencing, computational analysis plus a series of experimental validations, we report here that AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed, via forming a complex with AML1/ETO and via recruiting the cofactor. 4 ChIP-seq assays were used to identify the high confidence binding regions of AML1-ETO and AML1 in t(8;21) AML Kasumi-1 cell lines. The anti-AML1 (N20) antibody targets the N-terminus of AML1 and recognizes both AML1 and AML1/ETO; the anti-AML1 (C19) antibody targets the C-terminus of AML1 and recognizes AML1 but not AML1/ETO; the anti-ETO (C20) antibody targets the C-terminus of ETO and specifically recognizes AML1/ETO. 2 ChIP-seq assays were used to identify the binding regions of AML1 in human macrophage U937 cell lines. And the total input was used as control.

2015-11-04 | E-GEOD-65427 | biostudies-arrayexpress

Homo sapiens

Project description:AML1/ETO, AML1, and HEB binding patterns on chromosme 19

| PRJNA108837 | ENA

AML1/ETO binding pattern on human promoters

2008-12-22 | GSE10531 | GEO

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Project description:In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

2021-11-04 | PXD026374 | Pride

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