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

Karen Bunting, Sudha Rao, Kristine Hardy, Donna Woltring, Gareth S. Denyer, Jun Wang, Steve Gerondalds, M. Frances Shannon*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    93 Citations (Scopus)

    Abstract

    It is well established that the NF-κB 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-κB 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-κB/Rel sites in their proximal promoter regions. In addition, their promoters contain a higher average density of NF-κB/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-κB 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.

    Original languageEnglish
    Pages (from-to)7097-7109
    Number of pages13
    JournalJournal of Immunology
    Volume178
    Issue number11
    DOIs
    Publication statusPublished - 1 Jun 2007

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