The Small RNA Gene Activator Protein, SphI Postoctamer Homology-binding Factor/Selenocysteine tRNA Gene Transcription Activating Factor, Stimulates Transcription of the Human Interferon Regulatory Factor-3 Gene

Abstract

Many small nuclear RNA gene promoters are activated by SphI postoctamer homology (SPH)-binding factor/selenocysteine tRNA gene transcription activating factor (SBF/Staf). Whereas this transcription factor was initially identified by its ability to bind to SPH elements in such promoters, it was more recently shown to have the capacity to activate transcription of a synthetic mRNA gene promoter through a distinct activation domain. Here, we show that the human interferon regulatory factor-3 (IRF-3) gene promoter contains a functional SPH element that is bound by SBF/Staf in vitro and in transfected cells.

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

“…Furthermore, the number of identified targets is most likely underestimated because our screen was based solely on the SBS consensus and its variants, whereas other variant sites can also be bound by the protein. For example, we could not identify the IRF3 and AKR1A1 promoters present in DBTSS and known as hStaf/ ZNF143-dependent (12,15) because the SBS sequences in these promoters do not fit the queried sequences used in the various screens.…”

“…At the onset of this work, only seven promoters of protein coding genes were recognized as hStaf/ZNF143 targets (11)(12)(13)(14)(15)(16)(17). Among the 938 promoters identified in this study, 716 were obtained by queries at DBTSS (version 4), which contains only 8793 human promoters.…”

“…Eleven 18-bp-long sequences (A1 to K1 in Table 1) were used as queries for the first round of motif search. The 18-bp YYC-CCANNRNRCNNYRCR A1 sequence is the consensus derived by comparing the eight Staf motifs identified in seven human and mouse protein coding genes (11)(12)(13)(14)(15)(16)(17). It is more degenerated than the Staf consensus sequences derived from binding site selection experiments under moderately stringent conditions (see Introduction).…”

“…Indeed, although a 93-amino acid domain made of four repeat units is specialized for activating transcription from an mRNA promoter, a segment of only 18 amino acids acts specifically on snRNA and snRNA-type promoters (10). To date, only the following seven protein coding genes have been described to be regulated by hStaf/ZNF143: the cytosolic chaperonin containing t-complex polypeptide 1 (TCP1) (11); the interferon regulatory factor (IRF3) (12); the neuronal nitric-oxide synthase (NOS1) (13); the transaldolase (TALDO1) (14); the aldehyde reductase (AKR1A1) (15); the mitochondrial ribosomal protein S11 (MRPS11) (16); and the synaptobrevin-like 1 (SYBL1) (17).…”

Recruitment of RNA polymerase III to its target promoters

“…The presence of the latter type of activation domains in STAF and Oct-1 supports the idea that these proteins activate type 3 promoters (as well as RNA polymerase II snRNA promoters) in the cell. Indeed, both proteins have been localized to snRNA promoter sequences in vivo by chromatin immunoprecipitation experiments (Zhao et al 2001;Mach et al 2002). Thus, as for the core promoter sequences of type 3 promoters, the key factors recruited by the DSE are well characterized and are available in recombinant form.…”