EXPERIMENT_TITLE: GSM6509437: CEBPA_double_mutant_CHIC; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: CHi-C in primary AML cells was performed as described in Assi et al. (PMID: 30420649)
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Acute myeloid leukaemia (AML) is a heterogeneous haematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signalling genes. It is characterised by a disturbance of differentiation and abnormal proliferation of hematopoietic progenitors. We have previously shown that each AML subtype establishes its own core gene regulatory network, consisting of transcription factors binding to their target genes and imposing a specific gene expression pattern that is required for AML maintenance. In the study presented here, we integrate gene expression, open chromatin and ChIP data, with promoter-capture HiC data to define a refined core gene regulatory network common to all patients with one CEBPA N-terminal mutation plus one C- terminal mutation that each disrupt the structure of a major regulator of myelopoiesis (CEBPAN/C AML). We identify the binding sites of mutated C/EBPa proteins in primary cells, we show that the C/EBP family, AP-1 factors and RUNX1 colocalise and are all required for AML maintenance, and we employ single cell experiments to link important network nodes to the specific differentiation trajectory from leukemic stem to blast cells. Taken together, our study provides an important resource which predicts the specific therapeutic vulnerabilities of this AML sub-type in human cells. Overall design: Promoter capture HiC of an Acute Myeloid Leukemia patient with double CEBPA mutations
SAMPLE_TITLE: CEBPA_double_mutant_CHIC
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "CD34+ AML patient cells"}, {"TAG": "cell type", "VALUE": "CD34+ AML cells"}, {"TAG": "genotype", "VALUE": "CEBPA double mutant"}, {"TAG": "disease", "VALUE": "Acute Myeloid Leukemia"}]
Pool_Member_@attributes_sample_title: CEBPA_double_mutant_CHIC
RUN_SET_RUN_Pool_Member_@attributes_sample_title: CEBPA_double_mutant_CHIC
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