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Chromatin analysis of multiple myeloma cells following CBP/p300 inhibition and degradation (ATAC-Seq)

ABSTRACT: We performed ATAC-seq on MM.1S cells treated with A-485, GNE-781, and the combination of both, or with dCBP-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160333 | GEO | 2020/12/31

REPOSITORIES: GEO

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Chromatin analysis of multiple myeloma cells following CBP/p300 inhibition and degradation (ChIP-Seq)

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Chromatin analysis of multiple myeloma cells following CBP/p300 inhibition and degradation

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

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Transcription profiling of mouse multiple myeloma tumors and splenic B cells from transgenics overexpressing XBP-1s

Project description:Multiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy. Experiment Overall Design: In this study, we have explored the biological impact of sustained XBP-1s expression in the lymphoid system, anticipating that this genetic event would be a necessary component along with other MM-relevant oncogenes and tumor suppressor gene manipulations to generate a MM-prone mouse model. Unexpectedly, XBP-1s overexpression alone yielded an MGUS-MM disease bearing many features classical of the human disease on the clinical, pathological and molecular levels. Experiment Overall Design: We performed expression analysis of B cells derived from the spleen of 20-week old Emu-xbp-1s mice (n=5) and non-transgenic mice (n=5). Additionally, we analyzed the expression profiles from MM tumor cells arising in Emu-xbp-1s mice (n=6).

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