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

Karen Bunting, Sudha Rao, Kristine Hardy, Donna Woltring, Gareth Denyer, Jun Wang, Steve Gerondakis, Frances Shannon

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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

Fingerprint Dive into the research topics of 'Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel'. Together they form a unique fingerprint.

  • Cite this

    Bunting, K., Rao, S., Hardy, K., Woltring, D., Denyer, G., Wang, J., Gerondakis, S., & Shannon, F. (2007). Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel. Journal of Immunology, 178(11), 7097-7109. https://doi.org/10.4049/jimmunol.178.11.7097