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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma [HiChIP II]

ABSTRACT: H3K27ac HiChIP analysis was performed in multiple myeloma cell lines and primary sample to analyze active chromatin-chromatin interactions in myeloma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267003 | GEO | 2024/06/25

REPOSITORIES: GEO

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma [HiChIP I]

Project description:H3K27ac HiChIP analysis was performed in two multiple myeloma cell lines to analyze active chromatin-chromatin interactions in myeloma.

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

Project description:We identified a novel super-enhance-driven oncogene PPP1R15B overexpressed in multiple myeloma as compared to normal plasma cells and B lymphoma cells. Circular chromosome conformation capture sequencing (4C-seq) was used to confirm the interactions between PPP1R15B enhancer and promoter.

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma [HiChIP II]

Project description:Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma [HiChIP II]

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Project description:Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma [HiChIP I]

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

Project description:Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

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Super-enhancer-driven PPP1R15B/CReP, regulated by C/EBPβ and YY1, is oncogenic in multiple myeloma

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Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.

Project description:Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells. Our comprehensive transcriptomic and phenomic analyses prioritize candidate genes with biological and clinical implications in myeloma. We show that myeloma cells frequently acquire SE that transcriptionally activate an oncogene PPP1R15B, which encodes a regulatory subunit of the holophosphatase complex that dephosphorylates translation initiation factor eIF2α. Epigenetic silencing or knockdown of PPP1R15B activates pro-apoptotic eIF2α-ATF4-CHOP pathway, while inhibiting protein synthesis and immunoglobulin production. Pharmacological inhibition of PPP1R15B using Raphin1 potentiates the anti-myeloma effect of bortezomib. Our study reveals that myeloma cells are vulnerable to perturbation of PPP1R15B-dependent protein homeostasis, highlighting a promising therapeutic strategy.

| S-EPMC11316114 | biostudies-literature

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