A Genome Scale Location Analysis of Human Staf/ZNF143-binding Sites Suggests a Widespread Role for Human Staf/ZNF143 in Mammalian Promoters

Staf was originally identified as the transcriptional activator of Xenopus tRNASec and small nuclear (sn) RNA-type genes. Recently, transcription of seven human (h) protein coding genes was reported to be activated by the human ortholog hStaf/ZNF143. Here we have used a combined in silico and bioche...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-12, Vol.281 (52), p.39953-39962
Main Authors: Myslinski, Evelyne, Gérard, Marie-Aline, Krol, Alain, Carbon, Philippe
Format: Article
Language:English
Subjects:
Amino Acid Motifs - genetics
Animals
Base Sequence
Binding Sites - genetics
Chlorocebus aethiops
Computational Biology
Conserved Sequence
COS Cells
CpG Islands - genetics
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Genetic Variation
Genome, Human
Humans
Mice
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic - physiology
Trans-Activators - genetics
Trans-Activators - metabolism
Trans-Activators - physiology
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Summary:Staf was originally identified as the transcriptional activator of Xenopus tRNASec and small nuclear (sn) RNA-type genes. Recently, transcription of seven human (h) protein coding genes was reported to be activated by the human ortholog hStaf/ZNF143. Here we have used a combined in silico and biochemical approach to identify 1175 conserved hStaf/ZNF143-binding sites (SBS) distributed in 938 promoters of four mammalian genomes. The SBS shows a significant positional preference and occurs mostly within 200 bp upstream of the transcription start site. Chromatin immunoprecipitation assays with 295 of the promoters established that 90% contain bona fide SBS. By extrapolating the values of this mapping to the full sizes of the mammalian genomes, we can infer the existence of at least 2500 SBS distributed in 2000 promoters. This unexpected large number strongly suggests that SBS constitutes one of the most widespread transcription factor-binding sites in mammalian promoters. Furthermore, we demonstrated that the presence of the SBS alone is sufficient to direct expression of a luciferase reporter gene, suggesting that hStaf/ZNF143 can recruit per se the transcription machinery.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M608507200