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

Bunting, K; Rao, S; Hardy, K; Woltring, D; Denyer, GS; Wang, J; Gerondakis, S; Shannon, MF

Author(s): Bunting, K; Rao, S; Hardy, K; Woltring, D; Denyer, GS; Wang, J; Gerondakis, S; Shannon, MF;
Details: Publication Year 2007-06-01,Volume 178,Issue #11,Page 7097-7109
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: It is well established that the NF-kappa B 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-kappa B 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-kappa B/Rel sites in their proximal promoter regions. In addition, their promoters contain a higher average density of NF-kappa B/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-kappa B 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.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: GM-CSF PROMOTER; CRYSTAL-STRUCTURE; EXHIBIT DEFECTS; BINDING MOTIFS; FAMILY-MEMBERS; UP-REGULATION; MICE LACKING; ACTIVATION; PROTEINS; IDENTIFICATION
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Creation Date: 2007-06-01 12:00:00