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A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142494 | GEO | 2020/08/24

REPOSITORIES: GEO

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A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.

Project description: Not available

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A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition [Microarray]

Project description:The activated B-cell (ABC) to plasmablast transition is the cusp of antibody secreting cell (ASC) differentiation but is incompletely defined. We apply expression time-courses, parsimonious gene correlation network analysis, and ChIP-seq to explore this in human cells. The transition initiates with input signal loss leading within hours from cell growth dominant programs to enhanced proliferation, accompanied from 24h by ER-stress response, secretory optimization and upregulation of ASC features. Clustering of genomic occupancy for ASC transcription factors (TFs) IRF4, BLIMP1 and XBP1 with CTCF and histone marks defines distinct patterns for each factor in plasmablasts. Integrating TF-associated clusters and modular gene expression identifies a dichotomy: XBP1 and IRF4 significantly link to gene modules induced in plasmablasts, but not to modules of repressed genes, while BLIMP1 links to modules of ABC genes repressed in plasmablasts but is not significantly associated with modules induced in plasmablasts. Pharmacological inhibition of the G9A (EHMT2) histone-methytransferase, a BLIMP1 co-factor that catalyzes repressive H3K9me2 marks, leaves functional ASC differentiation intact but de-represses ABC-state genes. Thus, in human plasmablasts IRF4 and XBP1 emerge as the dominant association with ASC gene expression, while BLIMP1 links to repressed modules with particular focus in repression of the B-cell activation state.

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A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition [ChIP-seq]

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A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition

Project description:A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition

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