Distribution of NF-kappaB-binding sites across human chromosome 22.
We have mapped the chromosomal binding site distribution of a transcription factor in human cells. The NF-kappaB family of transcription factors plays an essential role in regulating the induction of genes involved in several physiological processes, including apoptosis, immunity, and inflammation. The binding sites of the NF-kappaB family member p65 were determined by using chromatin immunoprecipitation and a genomic microarray of human chromosome 22 DNA. Sites of binding were observed along the entire chromosome in both coding and noncoding regions, with an enrichment at the 5' end of genes. Strikingly, a significant proportion of binding was seen in intronic regions, demonstrating that transcription factor binding is not restricted to promoter regions. NF-kappaB binding was also found at genes whose expression was regulated by tumor necrosis factor alpha, a known inducer of NF-kappaB-dependent gene expression, as well as adjacent to genes whose expression is not affected by tumor necrosis factor alpha. Many of these latter genes are either known to be activated by NF-kappaB under other conditions or are consistent with NF-kappaB's role in the immune and apoptotic responses. Our results suggest that binding is not restricted to promoter regions and that NF-kappaB binding occurs at a significant number of genes whose expression is not altered, thereby suggesting that binding alone is not sufficient for gene activation.
Martone
Rebecca
R
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8005, USA.
Euskirchen
Ghia
G
Bertone
Paul
P
Hartman
Stephen
S
Royce
Thomas E
TE
Luscombe
Nicholas M
NM
Rinn
John L
JL
Nelson
F Kenneth
FK
Miller
Perry
P
Gerstein
Mark
M
Weissman
Sherman
S
Snyder
Michael
M
D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics* / Q000378:metabolism*; D016384:Consensus Sequence; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D016328:NF-kappa B / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000494:pharmacology; D051996:Transcription Factor RelA; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha