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Ca2+ influx through ORAI1 and ORAI2 channels regulates chromatin accessibility in CD4+ T cells

ABSTRACT: Activation of CD4+ T cells by T cell receptor (TCR) signaling results in altered gene expression as a result of epigenetic and transcriptional regulation. A critical TCR signaling pathway in CD4+ T cells is driven by Ca2+ influx across the plasma membrane through Ca2+ release-activated Ca2+ (CRAC) channels that are formed by ORAI1 and ORAI2 proteins. Here we analyzed the effects of suppressing Ca2+ influx in mouse CD4+ T cells on chromatin accessibility by genetically deleting the ORAI1 channel alone or both ORAI1 and ORAI2 channels. CD4+ T cells specific for ovalbumin (OVA) from TCR transgenic OT-II were activated by in vivo exposure to influenza A virus (IAV) expressing OVA neoantigen. Changes in chromatin accessibility of CD4+ T cells in response to IAV-OVA infection were determined by ATAC sequencing

ORGANISM(S): Mus musculus

PROVIDER: GSE253187 | GEO | 2025/01/01

REPOSITORIES: GEO

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Ca2+ influx through ORAI1 and ORAI2 channels regulates chromatin accessibility in CD4+ T cells

Project description:Ca2+ influx through ORAI1 and ORAI2 channels regulates chromatin accessibility in CD4+ T cells

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Project description:We showed that the overexpression of ORAI1 in the neurons of murine brain leads to spontaneous occurrence of seizure-like events in aged animals. We aimed to identify the mechanism responsible for this phenomenon. Using modified Ca2+-addback assay in the slices of CA1 hippocampal region and FURA-2AM calcium indicator we found that overexpression of ORAI1 in neurons leads to altered Ca2+ response. Next, by RNASeq we identified set of genes, whose expression was changed in FVB/NJ-Tg(ORAI1)Ibd mice.

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