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

66 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

NF-kappa B
rel Genes
Transcription Factors
Genome
T-Lymphocytes
Gene Expression
Genes
Luciferases
Genetic Promoter Regions
3'-(1-butylphosphoryl)adenosine
Cell Survival
Polymerase Chain Reaction
DNA
Growth

Cite this

Bunting, Karen ; Rao, Sudha ; Hardy, Kristine ; Woltring, Donna ; Denyer, Gareth ; Wang, Jun ; Gerondakis, Steve ; Shannon, Frances. / Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel. In: Journal of Immunology. 2007 ; Vol. 178, No. 11. pp. 7097-7109.
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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",
author = "Karen Bunting and Sudha Rao and Kristine Hardy and Donna Woltring and Gareth Denyer and Jun Wang and Steve Gerondakis and Frances Shannon",
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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, vol. 178, no. 11, pp. 7097-7109. https://doi.org/10.4049/jimmunol.178.11.7097

Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel. / Bunting, Karen; Rao, Sudha; Hardy, Kristine; Woltring, Donna; Denyer, Gareth; Wang, Jun; Gerondakis, Steve; Shannon, Frances.

In: Journal of Immunology, Vol. 178, No. 11, 2007, p. 7097-7109.

Research output: Contribution to journalArticle

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AU - Bunting, Karen

AU - Rao, Sudha

AU - Hardy, Kristine

AU - Woltring, Donna

AU - Denyer, Gareth

AU - Wang, Jun

AU - Gerondakis, Steve

AU - Shannon, Frances

PY - 2007

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N2 - 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

AB - 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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DO - 10.4049/jimmunol.178.11.7097

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