title: Calcium mobilization is both required and sufficient for initiating chromatin decondensation during activation of peripheral T-cells.
abstract: Antigen engagement of the T-cell receptor (TCR) induces a rapid and dramatic decondensation of chromatin that is necessary for T-cell activation. This decondensation makes T-cells competent to respond to interleukin-2 providing a mechanism to ensure clonotypic proliferation during an immune response. Using murine T-cells, we investigated the mechanism by which TCR signaling can initiate chromatin decondensation, focusing on the role of calcium mobilization. During T-cell activation, calcium is first released from intracellular stores, followed by influx of extracellular calcium via store operated calcium entry. We show that mobilization of intracellular calcium is required for TCR-induced chromatin decondensation. However, the decondensation is not dependent on the activity of the downstream transcription factor NFAT. Furthermore, we show that the influx of extracellular calcium is dispensable for initiating chromatin decondensation. Finally, we show that mobilization of calcium from intracellular stores is sufficient to induce decondensation, independent of TCR engagement. Collectively, our data suggest that chromatin decondensation in peripheral T-cells is controlled by modulating intracellular calcium levels.
authors.affiliation: Department of Biology, Furman University, Greenville, SC 29613, USA.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Lee
authors.affiliation: Department of Biology, Furman University, Greenville, SC 29613, USA.
authors.forename: Kellie N
authors.initials: KN
authors.lastname: Bingham
authors.affiliation: Department of Biology, Furman University, Greenville, SC 29613, USA.
authors.forename: Taylor Y
authors.initials: TY
authors.lastname: Mitchell
authors.affiliation: Department of Biology, Furman University, Greenville, SC 29613, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Meredith
authors.affiliation: Department of Biology, Furman University, Greenville, SC 29613, USA. Electronic address: jason.rawlings@furman.edu.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Rawlings
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002843:Chromatin / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D002843:Chromatin; D004075:Diglycerides; D050778:NFATC Transcription Factors; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium
keywords: Calcium; Chromatin decondensation; NFAT; T-cell activation