Protein binding profiles on chromatin in human AML cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA664746 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12682541_1.fastq.gz | Fastqsanger.gz | |||
| SRR12682541_2.fastq.gz | Fastqsanger.gz | |||
| SRR12682542_1.fastq.gz | Fastqsanger.gz | |||
| SRR12682542_2.fastq.gz | Fastqsanger.gz | |||
| SRR12682543_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 92 |
Similar Datasets
Project description:IRF8 binding profiles in human AML cells
| PRJNA662301 | ENA
Project description:Cancer cell type-selective addiction of transcription-chromatin regulatory program provides opportunities for therapeutic interventions. Here, we uncovered an IRF8-MEF2D transcription factor (TF) regulatory circuit as an acute myeloid leukemia (AML)-biased dependency. Combining CRISPR-based genetic screens, transcriptional analysis, and chromatin profiling, we demonstrated that a chromatin regulator, ZMYND8, directly regulates IRF8 and MYC expression through occupying AML-specific enhancer regions. ZMYND8 was essential for AML proliferation both in vitro and in vivo. The ZMYND8-occupied IRF8 enhancer was further characterized using Circular Chromosome Conformation Capture and CRISPRi-based perturbation assays and was observed in primary patient cells. Importantly, mutagenesis experiments revealed that the PHD/Bromodomain/PWWP reader module is required for ZMYND8 tethering to leukemia-essential co-activator BRD4 for enhancer-mediated gene regulation. Our results rationalize ZMYND8 as a potential selective therapeutic target for modulating the IRF8/MYC transcriptional networks in AML.
2021-09-06 | GSE158282 | GEO
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
Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. This SuperSeries is composed of the following subset Series: GSE29222: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding [ChIP-Seq and DNAse-Hypersensitivity data] GSE29223: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding [expression array data] GSE34540: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding (ChIP-seq) GSE34594: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding (Illumina expression) Refer to individual Series
2012-03-26 | E-GEOD-29225 | biostudies-arrayexpress
Project description:Cancer cell type-selective addiction of transcription-chromatin regulatory program provides opportunities for therapeutic interventions. Here, we uncovered an IRF8-MEF2D transcription factor (TF) regulatory circuit as an acute myeloid leukemia (AML)-biased dependency. Combining CRISPR-based genetic screens, transcriptional analysis, and chromatin profiling, we demonstrated that a chromatin regulator, ZMYND8, directly regulates IRF8 and MYC expression through occupying AML-specific enhancer regions. ZMYND8 was essential for AML proliferation both in vitro and in vivo. The ZMYND8-occupied IRF8 enhancer was further characterized using Circular Chromosome Conformation Capture and CRISPRi-based perturbation assays and was observed in primary patient cells. Importantly, mutagenesis experiments revealed that the PHD/Bromodomain/PWWP reader module is required for ZMYND8 tethering to leukemia-essential co-activator BRD4 for enhancer-mediated gene regulation. Our results rationalize ZMYND8 as a potential selective therapeutic target for modulating the IRF8/MYC transcriptional networks in AML.
2021-09-06 | GSE157631 | GEO
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.
2012-09-18 | GSE23730 | GEO
Project description:1. evaluation of diagnostic importance of insulin like growth factor binding protein3 in patient with recently diagnosed as Colorectal cancer
2. correlation between the diagnostic efficacy of insulin like growth factor binding protein 3 with routine marker carcinoembryonic antigen.
| 59449 | ecrin-mdr-crc
Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. RUNX1 siMM and RUNX1 siRE ChIP-Seq samples and a paired-end ChIP-Seq samples from patients with t(8;21) AML are used in this study; there are two paired-end ChIP-Seq runs and control per patient
2012-03-27 | E-GEOD-34540 | biostudies-arrayexpress
Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. Total RNA were obtained using 8 samples over four time courses (mismatch control and knock-down)
2012-03-27 | E-GEOD-29223 | biostudies-arrayexpress
Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. Total RNA were obtained using 8 samples over a time course of 10 days or using two samples two days after siRNA electroporation (mismatch control siRNA and RUNX1/ETO knock-down)
2012-03-27 | E-GEOD-34594 | biostudies-arrayexpress