Upstream activating sequence

About: Upstream activating sequence is a research topic. Over the lifetime, 1633 publications have been published within this topic receiving 100112 citations.

Regulation of entry into gametogenesis by Ste11: the endless game

Abstract: Sexual reproduction is a fundamental aspect of eukaryotic cells, and a conserved feature of gametogenesis is its dependency on a master regulator. The ste11 gene was isolated more than 20 years ago by the Yamamoto laboratory as a suppressor of the uncontrolled meiosis driven by a pat1 mutant. Numerous studies from this laboratory and others have established the role of the Ste11 transcription factor as the master regulator of the switch between proliferation and differentiation in fission yeast. The transcriptional and post-transcriptional controls of ste11 expression are intricate, but most are not redundant. Whereas the transcriptional controls ensure that the gene is transcribed at a high level only when nutrients are rare, the post-transcriptional controls restrict the ability of Ste11 to function as a transcription factor to the G1-phase of the cell cycle from where the differentiation programme is initiated. Several feedback loops ensure that the cell fate decision is irreversible. The complete panel of molecular mechanisms operating to warrant the timely expression of the ste11 gene and its encoded protein basically mirrors the advances in the understanding of the numerous ways by which gene expression can be modulated. Abbreviations: CTD, C-terminal domain; HMG, high-mobility group; MAPK, mitogen-activated protein kinase; PKA, cAMP-dependent protein kinase; SAGA, Spt–Ada–Gcn5–acetyltransferase; Tor, target of rapamycin; TORC1, target of rapamycin complex 1; UASst, upstream activating sequence for ste11

CodY-Mediated Regulation of Guanosine Uptake in Bacillus subtilis

Abstract: CodY is a global transcriptional regulator known to control expression of more than 100 genes and operons in Bacillus subtilis. Some of the most strongly repressed targets of CodY, the nupNOPQ (formerly, yufNOPQ ) genes, were found to encode a guanosine transporter. Using DNase I footprinting experiments, we identified two high-affinity CodY-binding sites in the regulatory region of the nupN gene. The two sites are located 50 bp upstream and 163 bp downstream of the transcription start site. The downstream site was responsible for 6- to 8-fold nupN repression in the absence of the upstream site. When the upstream site was intact, however, only a minor contribution of the downstream site to nupN regulation could be detected under the conditions tested. Both sites contained 15-bp CodY-binding motifs with two mismatches each with respect to the consensus sequence, AATTTTCWGTTTTAA. However, the experimentally determined binding sites included additional sequences flanking the 15-bp CodY-binding motifs. An additional version of the 15-bp CodY-binding motif, with 5 mismatches with respect to the consensus but essential for efficient regulation by CodY, was found within the upstream site. The presence of multiple 15-bp motifs may be a common feature of CodY-binding sites.

ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells

Abstract: The aim of this study has been to identify transcription factors involved in transcriptional regulation of the human SOX18 gene expression. Structural analysis revealed that the SOX18 promoter lacks a TATA box, but is CG-rich containing many putative binding sites for transcription factors that can bind and act through GC-boxes. Alignment analysis of promoter regions between human and mouse revealed conserved putative binding sites for transcription factors NF-Y and Sp-family members. Mithramycin A treatment led to increased SOX18 expression in vivo raising the possibility that the GC-rich sequence of the human SOX18 promoter might be occupied by transcription factor(s) that acts as repressor(s). Using in vitro binding assays we have demonstrated that transcription factors Sp3, ZBP-89 and NF-Y are capable of binding to the SOX18 promoter region spanning the sequence −200 to −162 relative to ATG and that formation of complexes could be efficiently reduced by mithramycin A. Furthermore, co-transfection experiments revealed that over-expression of Sp3 and ZBP-89 down-regulate, while over-expression of NF-Y up-regulates SOX18 promoter activity in HeLa cells. The involvement of these transcription factors in the regulation of SOX18 expression in HeLa cells was further confirmed in vivo by Western blot analyses. In this paper, for the first time, we have demonstrated that Sp3, ZBP-89 and NF-Y are involved in transcriptional regulation of the human SOX18 gene expression. Presented data provide the initial information about transcriptional regulation that will help in better understanding of molecular mechanisms involved in regulation of SOX18 gene expression.