Transcriptional regulation by Poly(ADP-ribose) polymerase-1 during T cell activation
1 Transplant Unit, Department of Surgery, University Hospital "Virgen de la Arrixaca", University of Murcia, Ciberehd, Murcia, Spain
2 Bioinformatics and Genomics Program, Centre for Genomic Regulation, PRBB, Barcelona, Spain
3 Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, Murcia, Spain
4 Department of Immunology, IMIM-Hospital del Mar, PRBB, Barcelona, Spain
5 Plataforma de Bioinformática, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clinic, Barcelona, Spain
BMC Genomics 2008, 9:171 doi:10.1186/1471-2164-9-171Published: 16 April 2008
Accumulating evidence suggests an important role for the enzyme poly(ADP-ribose) polymerase-1 (PARP-1) as an integral part of the gene expression regulatory machinery during development and in response to specific cellular signals. PARP-1 might modulate gene expression through its catalytic activity leading to poly(ADP-ribosyl)ation of nuclear proteins or by its physical association with relevant proteins. Recently, we have shown that PARP-1 is activated during T cell activation. However, the proposed role of PARP-1 in reprogramming T cell gene expression upon activation remains largely unexplored.
In the present study we use oligonucleotide microarray analysis to gain more insight into the role played by PARP-1 during the gene expression reprogramming that takes place in T cells upon activation with anti-CD3 stimulation alone, or in combination with anti-CD28 co-stimulation. We have identified several groups of genes with expression modulated by PARP-1. The expression of 129 early-response genes to anti-CD3 seems to be regulated by PARP-1 either in a positive (45 genes) or in a negative manner (84 genes). Likewise, in the presence of co-stimulation (anti-CD3 + anti-CD28 stimulation), the expression of 203 genes is also regulated by PARP-1 either up (173 genes) or down (30 genes). Interestingly, PARP-1 deficiency significantly alters expression of genes associated with the immune response such as chemokines and genes involved in the Th1/Th2 balance.
This study provides new insights into changes in gene expression mediated by PARP-1 upon T cell activation. Pathway analysis of PARP-1 as a nuclear signalling molecule in T cells would be of relevance for the future development of new therapeutic approaches targeting PARP-1 in the acquired immune response.