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J. Biol. Chem., Vol. 281, Issue 52, 39953-39962, December 29, 2006

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

From the Institut de Biologie Moléculaire et Cellulaire, UPR CNRS Architecture et Réactivité de l'ARN, Université Louis Pasteur, 15 Rue René Descartes, 67084 Strasbourg Cedex, France

Staf was originally identified as the transcriptional activator of Xenopus tRNA^Sec 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.

Received for publication, September 5, 2006 , and in revised form, November 7, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) NM_003085 [GenBank] , NM_001320 [GenBank] , NM_006185 [GenBank] , NM_004748 [GenBank] , NM_012257 [GenBank] , and NM_005111.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Fig. S1.

¹ To whom correspondence should be addressed. Tel.: 33-3-88-41-70-64; Fax: 33-3-88-60-22-18; E-mail: P.Carbon{at}ibmc.u-strasbg.fr.

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