Transcriptomics

Dataset Information

4

Enhancers of Polycomb 1 & 2 in normal and leukaemic haematopoiesis


ABSTRACT: A knockdown screen of chromatin regulatory genes in human THP1 MLL-AF9 AML cells identified EPC1 and EPC2 as required for cell survival. Normal myeloid progenitor cells did not require EPC1 or EPC2 for their function. To determine the transcriptional consequences of EPC knockdown, normal murine granulocyte-macrophage progenitor (GMP) cells, or murine MLL-AF9 AML GMP-like cells, were FACS purified from mice and infected with lentiviral vectors targeting EPC1 or EPC2 for knockdown, or a non-tageting control. 42 hours later knockdown or control cells were FACS purified and exon array analysis was performed on the sorted populations. For normal GMP cells, three biological replicates (three separate animals) each of control cells, EPC1 knockdown cells and EPC2 knockdown cells; for MLL-AF9 AML GMP-like cells cells, three biological replicates (three separate leukaemias) each of control cells, EPC1 knockdown cells and EPC2 knockdown cells.

ORGANISM(S): Mus musculus  

SUBMITTER: Tim C Somervaille  

PROVIDER: E-GEOD-39172 | ArrayExpress | 2013-10-30

SECONDARY ACCESSION(S): GSE39172PRJNA170138

REPOSITORIES: GEO, ArrayExpress

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Publications

Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells.

Huang X X   Spencer G J GJ   Lynch J T JT   Ciceri F F   Somerville T D D TD   Somervaille T C P TC  

Leukemia 20131029 5


Through a targeted knockdown (KD) screen of chromatin regulatory genes, we identified the EP400 complex components EPC1 and EPC2 as critical oncogenic cofactors in acute myeloid leukemia (AML). EPC1 and EPC2 were required for the clonogenic potential of human AML cells of multiple molecular subtypes. Focusing on MLL-mutated AML as an exemplar, Epc1 or Epc2 KD-induced apoptosis of murine MLL-AF9 AML cells and abolished leukemia stem cell potential. By contrast, normal hematopoietic stem and proge  ...[more]

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