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Transcriptome profiling of H3K27me3 demethylase deficient B cells

ABSTRACT: To assess how H3K27me3 demethylases, UTX and JMJD3, regulate B cell and plasma cell trasncriptomes. RNA-seq was performed on the following populations from control (CreCtrl) and double knockout (dKO) mice: 1) naïve marginal zone B (MZB) cells and follicular B (FOB) cells from control (CreCtrl) and double knockout (dKO) mice, 2) PC generated after three days of ex vivo culture of MZB or FOB cells, 3) PC generated at three days post in vivo stimulation with LPS

ORGANISM(S): Mus musculus

PROVIDER: GSE185095 | GEO | 2022/02/01

REPOSITORIES: GEO

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Accessible chromatin profiling of H3K27me3 demethylase deficient B cells

Project description:To understand the role of the H3K27me3 demethylases, UTX and JMJD3, in regulating chromatin accessibility. ATAC-seq was performed on the following populations from control (CreCtrl) and double knockout (dKO) mice: naïve marginal zone B cells and follicular B cells as well plasma cell generated at three days post in vivo stimulation with LPS.

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H3K27me3 localization in UTX deficient Plasma cells by CUT&Tag

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H3K27me3 localization in UTX deficient Plasma cells by ChIP-seq

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2022-02-01 | GSE185097 | GEO

Gene expression profiling in mature OT-II TCR transgenic CD4 SP thymocytes, either Jmjd3- and Utx-deficient or -sufficient.

Project description:The biological functions of histone demethylases Jmjd3 and Utx remain poorly understood. We assessed such functions in developing T cells, using conditional (CD4-Cre-mediated) gene disruption, by inactivating Kdm6a and Kdm6b, respectively encoding Utx and Jmjd3, in immature CD4+CD8+ thymocytes. We compared microarray gene expression in mature (Va2hi CD24lo) mutant and wild-type CD4+CD8- thymocytes carrying the OT-II TCR transgene. We show that Jmjd3 and Utx redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Mature (Va2hi CD24lo) CD4 thymocytes were sorted from freshly prepared single-cell suspensions OT-II TCR transgenic thymocytes deficient for Utx and Jmjd3 (dKO, CD4-Cre conditional deletion of floxed Kdm6a and Kdm6b alleles), and from Cre-negative controls (wild-type). Total RNA was extracted from sorted thymocytes using the RNeasy Plus Mini Kit (Qiagen) and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturer’s recommendation. Data is generated from 3 replicates from each experiment.

2015-09-17 | E-GEOD-70363 | biostudies-arrayexpress

Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells

Project description:The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation and protein synthesis. Furthermore, Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally, Gclc deficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. In summary, Gclc is required to ensure the development of MZB, the integrity of the mitochondrial ETC in FoB and it is crucial for antibody-mediated immunity.

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2015-05-17 | E-GEOD-47081 | biostudies-arrayexpress

Impact of Jmjd3 and Utx histone demethylases on Histone H3 lysine 27 trimethylation (H3K27Me3) in mature CD4 SP thymocytes

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2015-09-02 | E-GEOD-70795 | biostudies-arrayexpress

UTX and JMDJ3 regulate NKT development

2015-05-17 | GSE47081 | GEO

Ezh2, Utx and Jmjd3 deletion on the H3k27me3 level in mouse chondrocytes

Project description:The level of H3K27me3 were examined by conditional knockout Ezh2, Utx or Jmjd3 in mouse chondrocyte

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Chemical Inhibition of H3K27me3 demethylases during B cell differentiation

Project description:To understand the role of the H3K27me3 demethylases, UTX and JMJD3, in B cell differentiation. Naïve B cells were cultures ex vivo with LPS, IL-2,IL-5 in the presence of DMSO or GSK-J4, UTX/JMJD3 inhibitor. Plasmablasts and activated B cells were magnetically enriched after 3 days of culture.

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