Promoter-specific activation of RNA polymerase II transcription by Sp1

doi:10.1016/0968-0004(86)90226-4

Trends in Biochemical Sciences

Volume 11, Issue 1, January 1986, Pages 20-23

https://doi.org/10.1016/0968-0004(86)90226-4 Get rights and content

Abstract

The RNA polymerase II transcription factor Sp1 is a protein that binds to specific DNA sequences and activates RNA synthesis from a select group of promoters. Sp1 and related factors appear to be important for modulation of gene expression in higher organisms.

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The Specificity protein 1 (Sp1) transcription factor
2020, An Innovative Approach to Understanding and Treating Cancer: Targeting pH: From Etiopathogenesis to New Therapeutic Avenues
Specificity protein 1 (Sp1) is a transcription factor that activates/promotes/co-promotes or enhances the transcription of many genes related to normal development, as well as cancerization and cancer evolution. Six genes that are strongly related to malignization and important players in the pH-tome are enhanced by Sp1: HIF-1α, (hypoxia inducible factor 1 alpha), CAIX (carbonic anhydrase 9), NHE1 (sodium/ hydrogen exchanger 1), NaV1.5 (isoform of voltage gated sodium channel), V-ATPase proton pumps and basigin. Therefore, Sp1 is a good target for reversing the pH gradient inversion. This chapter will consider the evidence of Sp1’s involvement in cancer, in pH gradient inversion, and the means for down-regulating it with existing drugs. This section will also present an in-depth discussion of tolfenamic acid, an old pain reliever used for the treatment of migraine, with little or no toxicity.
Effects of in ovo injection of vitamin C on heat shock protein and metabolic genes expression
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Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick’s age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and −336 CpG site in HSP60 promoter and −1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around −389 and −336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around −1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.
Synthetic promoter for efficient and muscle-specific expression of exogenous genes
2019, Plasmid
Citation Excerpt :
To acquire synthetic promoters with activity and specificity high enough for therapeutic application, we speculated that the combination of multiple kinds of transcriptional motifs, instead of unique myogenic factors in SPc5–12 (Li et al., 2001; Zou et al., 2018), should be a better strategy. To address this issue, three kinds of transcriptional regulatory elements were rationally determined and nineteen representative motifs were carefully selected: i) eight muscle-specific elements were SRE (Coletti et al., 2016), MEF-1, MEF-2 (Li et al., 1999), MEF-3 (Hidaka et al., 1993), TEF-1 (Wang et al., 2015), Trex (Himeda et al., 2012), MPEX (Himeda et al., 2012; Himeda et al., 2010) and MAPF (Walsh, 1989); ii) five highly conserved elements were AP-1 (Schenk et al., 1994), AP-2 (Hajra et al., 1994), GATA-2 (Dorfman et al., 1992), TATA Box (Mogno et al., 2010) and CAAT box (Kadonaga et al., 1986); iii) six virus-derived motifs were 72 bp repeat sequence from SV40 enhancer (Van Gaal et al., 2011), 19 bp repeat sequence from CMV enhancer, 16 bp, 18 bp, 19 bp and 21 bp repeat sequences from CMV promoter (Stinski, 1992;Payne et al., 2017). After gradual evaluations, the promoter SP-301 was picked out from ~1200 synthetic promoters via in vitro (Fig. 1) and in vivo expression of different reporter genes (Figs. 2,3).
Synthetic promoters (SPs) have many advantages over their natural counterparts, especially with regard to transcriptional activity and tissue specificity. Here, we report a new strategy to construct SPs for efficient and muscle-specific gene expression. First, 19 nucleic acid motifs classified to 3 kinds of transcriptional regulatory elements were rationally selected. A recombinant promoter library was constructed by randomly assembling these motifs. Second, the transcriptional activities of ~1200 SPs were screened by intramuscular expression of several reporter genes in different cell lines for activity higher than that of the cytomegalovirus (CMV) promoter, with SP-301 finally identified as the strongest. A single intramuscular injection of mice with an SP-301 plasmid expressing mouse growth hormone releasing hormone accelerated mouse growth significantly over 24 days. Third, the muscle specificity of SP-301 was confirmed in transgenic mice. Finally, in comparison with the CMV promoter, SP-301 accelerated translocation and increased the level of plasmid in the nuclei of myoblast cells to a greater extent than in non-muscle cells. Altogether, the study has provided a more rational strategy to construct efficient and tissue-specific promoters, with the promoter SP-301 exhibiting promising potential for establishing an intramuscular gene expression system for therapeutic applications.
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A class of gene-regulatory elements called enhancers are the main mediators controlling quantitative, temporal and spatial gene expressions. In the course of evolution, the enhancer landscape of higher organisms such as mammals has become quite complex, exerting biological functions precisely and coordinately. In mammalian skeletal development, the master transcription factors Sox9, Runx2 and Sp7/Osterix function primarily through enhancers on the genome to achieve specification and differentiation of skeletal cells. Recently developed genome-scale analyses have shed light on multiple layers of gene regulations, uncovering not only the primary mode of actions of these transcription factors on skeletal enhancers, but also the relation of the epigenetic landscape to three-dimensional chromatin architecture. Here, we review findings on the emerging framework of gene-regulatory networks involved in skeletal development. We further discuss the power of genome-scale analyses to provide new insights into genetic diseases and regenerative medicine in skeletal tissues.

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Trends in Biochemical Sciences

ReviewPromoter-specific activation of RNA polymerase II transcription by Sp1

Abstract

Cell

Cell

Cell

Trends Genet.

Cell

Cell

Cell

Cell

Cell

Cell

Cell

Cell

Cell

Annu. Rev. Biochem.

Curr. Top. Micro. Immun.

Nature

Review
Promoter-specific activation of RNA polymerase II transcription by Sp1