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Publication : Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel.

First Author  Bunting K Year  2007
Journal  J Immunol Volume  178
Issue  11 Pages  7097-109
PubMed ID  17513759 Mgi Jnum  J:148668
Mgi Id  MGI:3846042 Doi  10.4049/jimmunol.178.11.7097
Citation  Bunting K, et al. (2007) Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel. J Immunol 178(11):7097-109
abstractText  It is well established that the NF-kappaB family of transcription factors serves a major role in controlling gene expression in response to T cell activation, but the genome-wide roles of individual family members remain to be determined. c-Rel, a member of the NF-kappaB family, appears to play a specific role in T cell function because T cells from c-Rel(-/-) animals are defective in their response to immune signals. We have used expression profiling to identify sets of genes that are affected by either deletion or overexpression of c-Rel in T cells. Very few of these genes exhibit a strong requirement for c-Rel; rather, c-Rel appears to modulate the expression of a large number of genes in these cells. The sets of c-Rel-affected genes are significantly enriched for genes containing consensus NF-kappaB/Rel sites in their proximal promoter regions. In addition, their promoters contain a higher average density of NF-kappaB/Rel sites compared with all genes represented on the microarrays. A transcriptional module comprised of two closely spaced c-Rel consensus sites is found with higher frequency in the c-Rel-affected gene sets and may represent an important control module for genes regulated by c-Rel or other NF-kappaB family members. We confirmed the importance of these findings on a subgroup of genes by using quantitative PCR to monitor gene expression as well as in vitro c-Rel/DNA binding assays and luciferase reporter assays. The c-Rel-regulated genes identified here support a role for c-Rel in inflammatory responses as well as in the promotion of cell growth and survival.
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