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Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [ATAC-seq]

ABSTRACT: In order to look at global chromatin accessibility in enzalutamide sensitive (V16D) and enzalutamide-resistant t-NEPC lines (MR42D), we treated these lines with enzalutamide or vehicle and performed an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq). Hyperaccessible regions in V16D were associated with metabolic pathways, whereas hyperaccesible regions in MR42D were associated with neuronal pathways, indicating that the chromatin conformation in these enzalutamide resistant cells is conducive to transdifferentiation to a neuronal t-NEPC phenotype.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147874 | GEO | 2021/06/22

REPOSITORIES: GEO

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Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [RNA-seq]

Project description:To identify mechanisms that contribute to lineage plasticity and t-NEPC, we focused on enza-resistant cell lines with persistent AR expression that have features of lineage plasticity, including high expression of NEPC markers: the MR42D and MR42F cell lines. We cultured these enzalutamide resistant lines, which are usually maintained in medium with enzalutamide, without enzalutamide for 72 hors to "washout" the effects of enzalutamide, and then either enzalutamide or vehicle was added back to the growing media for 24 hours. Enzalutamide sensitive lines LNCaP and V16D were treated with either enzalutamide or vehicle for 24 hours. Enzalutamide reversibly increased expression neuronal markers in MR42D and MR42F cells, but not enza-sentitive LNCaP and V16D cells, suggesting that the AR may negatively regulate neuronal gene expression in these t-NEPC cells. Moreover, bromodomain inhibitors (BETi) ARV-771 and JQ1 reduced expression of NEPC target genes in MR42D cells.

2021-06-22 | GSE147876 | GEO

Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [ChIP-seq]

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