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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [RNA-seq]

ABSTRACT: Posterior homeobox D genes, in particular HOXD13, are over-expressed by Ewing sarcoma, a tumor driven by the oncogenic fusion protein EWS-FLI1. Here, we have found that EWS-FLI1 maintains HOXD13 expression through a GGAA microsatellite enhancer in the developmental posterior HOXD regulatory domain. Activation of this enhancer is EWS-FLI1 dependent and epigenomic silencing of this region leads to loss of HOXD13 expression in Ewing sarcoma cells, but not in unrelated cells. To determine the function of HOXD13 activation in Ewing sarcoma we performed nascent RNA sequencing or RNA sequencing upon HOXD13 knockdown.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148494 | GEO | 2022/06/28

REPOSITORIES: GEO

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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [CITE-seq]

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2014-10-30 | E-GEOD-61944 | biostudies-arrayexpress

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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma

Project description:EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma

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Project description:We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. Mesenchymal stem cells (MSCs) and a Ewing sarcoma cell line (SKNMC) were analyzed by ATAC-seq. EWS-FLI1 was expressed in MSCs using a lentiviral vector (pLIV EWSFLI1 or pLIV empty vector control). * Raw data not provided for the MSC samples. *

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