Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk

Partnerzy

A. Travis Mark


Ostatnie publikacje
1.  Brignall R., Cauchy P., Bevington Sarah L., Gorman B., Pisco Angela O., Bagnall J., Boddington C., Rowe W., England H., Rich K., Schmidt L., Dyer Nigel P., Travis Mark A., Ott S., Jackson Dean A., Cockerill Peter N., Paszek P., Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells, JOURNAL OF IMMUNOLOGY, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1602033, Vol.199, No.8, pp.2652-2667, 2017

Streszczenie:
TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression. We found that these regions typically function as inducible enhancers. Many of these elements contain composite NFAT/AP-1 sites, which typically support cooperative binding, thus further reinforcing the need for cooperation between calcium and kinase signaling in the activation of genes in T cells. In contrast, treatment with PMA or ionomycin alone induces chromatin remodeling at far fewer regions (∼600 and ∼350, respectively), which mostly represent a subset of those induced by costimulation. This suggests that the integration of TCR signaling largely occurs at the level of chromatin, which we propose plays a crucial role in regulating T cell activation.

Afiliacje autorów:
Brignall R. - inna afiliacja
Cauchy P. - inna afiliacja
Bevington Sarah L. - inna afiliacja
Gorman B. - inna afiliacja
Pisco Angela O. - inna afiliacja
Bagnall J. - inna afiliacja
Boddington C. - inna afiliacja
Rowe W. - inna afiliacja
England H. - inna afiliacja
Rich K. - inna afiliacja
Schmidt L. - inna afiliacja
Dyer Nigel P. - inna afiliacja
Travis Mark A. - inna afiliacja
Ott S. - inna afiliacja
Jackson Dean A. - inna afiliacja
Cockerill Peter N. - inna afiliacja
Paszek P. - inna afiliacja

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