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Unraveling lineage specific transcription factors involved in the reprogramming of Neuroblastoma from self-renewal to differentiation state

ABSTRACT: Temporal regulation of super enhancer (SE) driven lineage specific transcription factors (TFs), underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify critical SEs driving TF regulators of NB, we utilized NB cells in which retinoid (RA) induces growth arrest and differentiation. H3K27ac ChIP-seq paired with RNA-seq over a time course of RA treatment revealed that SEs moving in a coordinated manner with four distinct temporal patterns (clusters). SEs that decreased with RA linked to 24 TFs involved in stem cell differentiation (MYCN, GATA3, SOX11). Three other TF SE clusters had sequential waves of activation at 2, 4 and 8 days of RA treatment and involved TFs regulating neural development (GATA2 and SOX4). Our study has identified candidate oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147408 | GEO | 2020/07/29

REPOSITORIES: GEO

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